0
Communications to the Editor |

Adrenal Suppression Related to Inhaled Corticosteroids Revisited FREE TO VIEW

Fernan Caballero-Fonseca, MD; Mario Sánchez-Borges, MD
Author and Funding Information

Affiliations: Caracas, Venezuela,  Antrim Hospital, Antrim, Northern Ireland

Correspondence to: Fernan Caballero-Fonseca, MD, Immunology Department, Centro Médico-Docente La Trinidad, Caracas, Venezuela



Chest. 2002;122(3):1103-1104. doi:10.1378/chest.122.3.1103
Text Size: A A A
Published online

To the Editor:

With growing concern, we read the report by Todd et al (October 2001 supplement)1about clinically significant adrenal suppression related to the administration of inhaled corticosteroids. That article and others, such as the one by Zimmerman et al,2have been linked to the use of the most potent of the inhaled corticosteroids, fluticasone, probably because of its well-known high lipophilicity, which confers a very high volume of distribution and a long plasmatic half-life.3Another report4 described a 6-year-old girl with obvious features of hypercortisolism who experienced an acute adrenal insufficiency episode that had been induced by the administration of budesonide after her treatment had been switched from fluticasone.

Earlier, in 1993, we had reported5 on a patient with similar clinical features. This child had been treated with customary doses of beclomethasone without any warning or evidence of hypercortisolism. All these reports were largely ignored and were considered to be extremely rare situations.

A few years later, Carrel et al6described the condition of a 3.5-year-old child who had been treated with a low dose of prednisone (2.5 mg every other day) and inhaled beclomethasone (255 μg/d) and who experienced an episode of severe hypoglycemia and cortisol deficiency that was virtually identical to that observed in our patient. At that time, this observation came to no surprise to us, since Tabachnik and Zadik7 also had reported severe adrenal suppression even at conventional steroid doses.

Recently, Lipworth8has repeatedly elaborated on the issue of adrenal suppression by inhaled fluticasone and has raised concerns about the probable large volume of distribution of mometasone furoate, despite previous claims for its very low (ie, < 1%) systemic bioavailability.9

In view of these observations, we encourage physicians to be aware of the possibility of systemic effects of inhaled corticosteroids in some asthmatic patients and of its clinical relevance, as these rare but very real events may occur not only with fluticasone treatment but also with all inhaled steroids that are currently on the market.

References

Todd, G, Buck, J, Ross-Russell, R, et al (2001) Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate [abstract].Chest120,139S. [CrossRef]
 
Zimmerman, B, Gold, M, Wherrett, D, et al Adrenal suppression in two patients with asthma treated with low dose of the inhaled steroid fluticasone propionate.J Allergy Clin Immunol1998;101,425-426. [PubMed]
 
Pedersen, S, O’Byrne, P A comparison of the efficacy and safety of inhaled corticosteroids in asthma.Allergy1997;52(suppl),1-34
 
Todd, GR, Wright, D, Ryan, M Acute adrenal insufficiency in a patient with asthma after changing from fluticasone propionate to budesonide.J Allergy Clin Immunol1999;103,956-957. [PubMed]
 
Caballero, F, Gunzler, P Severe adrenal suppression in a 12 year old induced by beclomethasone dipropionate [abstract]. J Allergy Clin Immunol. 1993;;91 ,.:261
 
Carrel, AL, Somers, S, Lemanske, RF, et al Hypoglycemia and cortisol deficiency associated with low-dose corticosteroid therapy for asthma.Pediatrics1996;97,921-923. [PubMed]
 
Tabachnik, E, Zadik, Z Diurnal cortisol secretion during therapy with inhaled beclomethasone dipropionate in children with asthma.J Pediatr1991;118,94-97
 
Lipworth, BJ Fluticasone and cortisol measurements.Chest2001;119,984-985. [PubMed]
 
Lipworth, BJ Mometasone furoate levels.Chest2001;120,1034-1035. [PubMed]
 
To the Editor:

We thank Doctors Caballero-Fonseca and Sanchez-Borges for their interest in our abstract (October 2001 supplement).1 We reported on a large case series of patients who had experienced acute adrenal crisis due to inhaled steroids, nearly all due to fluticasone (> 94%). Acute adrenal crisis was an extremely rare phenomenon before the introduction of fluticasone in the United Kingdom in 1994. We believe that our study highlighted important differences among the inhaled corticosteroid agents, and it specifically opposes the view that the most recently introduced inhaled steroid, fluticasone, has the best benefit/risk ratio.

However, we would like to emphasize that all the authors of our article are very enthusiastic prescribers of inhaled steroids as a first-line treatment for patients with all but the mildest forms of asthma. Inflammatory processes are absolutely fundamental to the pathogenesis of asthma, and inhaled steroids are by far the most effective drugs at reducing inflammation in asthma patients. They are also the most effective drugs at reducing the burden of asthma (ie, improving exercise tolerance, reducing days lost from school, preventing acute exacerbations, preventing hospital admissions, and decreasing the risk of death from asthma). In the vast majority of patients, the benefits greatly outweigh the risks. For example, in a long-term study (mean study duration, 9.92 years) of budesonide treatment (patient age range, 3 to 13 years) with a mean daily dose of 412 μg/d (dose range, 110 to 887 μg/d), there was no effect on final adult height and no evidence of any other significant side effects.2 This is most compelling and reassuring evidence of the long-term safety at least of this particular inhaled steroid in children.

We therefore believe in the early introduction of inhaled steroids in adequate dosages for the control of asthma, as is advised by all national and international guidelines, and that the safest amount of an inhaled steroid to administer to any child is the minimum amount required to control the asthma. Under these circumstances, the benefits of inhaled steroids greatly outweigh the morbidity and mortality associated with uncontrolled asthma. For example, it is important to remember that since the introduction of inhaled budesonide > 20 years ago, there have been > 10 billion patient-days of use of this drug, and reported serious side effects have been extremely rare. What other drug that we prescribe can claim such a safety record?

References
Todd, G, Buck, J, Ross-Russell, R, et al Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate [abstract]. Chest. 2001;;120 ,.:139S. [CrossRef]
 
Agertoft, L, Pedersen, S Effect of long-term treatment with inhaled budesonide on adult height in children with asthma.N Engl J Med2000;343,1064-1069. [PubMed]
 

Figures

Tables

References

Todd, G, Buck, J, Ross-Russell, R, et al (2001) Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate [abstract].Chest120,139S. [CrossRef]
 
Zimmerman, B, Gold, M, Wherrett, D, et al Adrenal suppression in two patients with asthma treated with low dose of the inhaled steroid fluticasone propionate.J Allergy Clin Immunol1998;101,425-426. [PubMed]
 
Pedersen, S, O’Byrne, P A comparison of the efficacy and safety of inhaled corticosteroids in asthma.Allergy1997;52(suppl),1-34
 
Todd, GR, Wright, D, Ryan, M Acute adrenal insufficiency in a patient with asthma after changing from fluticasone propionate to budesonide.J Allergy Clin Immunol1999;103,956-957. [PubMed]
 
Caballero, F, Gunzler, P Severe adrenal suppression in a 12 year old induced by beclomethasone dipropionate [abstract]. J Allergy Clin Immunol. 1993;;91 ,.:261
 
Carrel, AL, Somers, S, Lemanske, RF, et al Hypoglycemia and cortisol deficiency associated with low-dose corticosteroid therapy for asthma.Pediatrics1996;97,921-923. [PubMed]
 
Tabachnik, E, Zadik, Z Diurnal cortisol secretion during therapy with inhaled beclomethasone dipropionate in children with asthma.J Pediatr1991;118,94-97
 
Lipworth, BJ Fluticasone and cortisol measurements.Chest2001;119,984-985. [PubMed]
 
Lipworth, BJ Mometasone furoate levels.Chest2001;120,1034-1035. [PubMed]
 
Todd, G, Buck, J, Ross-Russell, R, et al Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate [abstract]. Chest. 2001;;120 ,.:139S. [CrossRef]
 
Agertoft, L, Pedersen, S Effect of long-term treatment with inhaled budesonide on adult height in children with asthma.N Engl J Med2000;343,1064-1069. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543