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• Budesonide cases should not have been included
  Jarl Ingelf
  Published on: 8 November 2001
• Systemic effects of inhlaed corticosteroids
  Ranjan Suri
  Published on: 23 October 2001

• Published on: 8 November 2001

  Budesonide cases should not have been included

  • Jarl Ingelf, Medical Affairs Specialist

  Dear Editor,

  In this short report, Patel et al. presents a series of eight cases of ”symptomatic adrenal insufficiency during inhaled corticosteroid treatment” [1]. The paper highlights several interesting points. However, the determination of cases as “symptomatic”, the laboratory investigations performed to establish the diagnosis, and the selection of cases, can be seriously questioned.

  The a...

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  Dear Editor,

  In this short report, Patel et al. presents a series of eight cases of ”symptomatic adrenal insufficiency during inhaled corticosteroid treatment” [1]. The paper highlights several interesting points. However, the determination of cases as “symptomatic”, the laboratory investigations performed to establish the diagnosis, and the selection of cases, can be seriously questioned.

  The authors have considered a poor growth in height and weight as a symptom of adrenal insufficiency. In the discussion, they state that systemic effect of conventional doses of inhaled corticosteroids will result in increased or normal weight gain, while a poor weight gain/weight is assumed to indicate an adrenal insufficiency. This assumption is in our opinion not reasonable to make.

  As can be calculated from Table 1 in their report, the average deviation over time in weight is smaller (–0.66 SDS), compared to the average deviation in height (–0.74 SDS). The observed weight deviation may be secondary to the deviation in height, which is an unusual but well described side effect to ICS, during the first years of treatment.

  Difference in SDS between first and second measurement up to the diagnosis of adrenal insufficiency, as calculated from figures given in

  Table (1):

  Case	Height SDS	Weight SDS
  1	*	*
  2	1.00	0.90
  3	0.00	0.70
  4	1.30	0.70
  5	0.20	0.30
  6	1.40	1.80
  7	0.60	0.10
  8	0.70	0.10
  Average	0.74	0.66

  * not assessable

  The laboratory investigations performed to establish the diagnosis are in two cases uncertain. Except during an acute adrenal crisis, basal plasma and/or urinary steroid levels are not sufficient to give a definitive diagnosis of adrenal insufficiency [2]. This is especially important in the case of exogenous steroid exposure, where adrenal adaptation to systemic levels of inhaled glucocorticosteroids occurs as a way to protect against systemic effects of exogenous steroids [3]. To determine adrenal function in such patients, dynamic test with ACTH is necessary. In the report by Patel et al., standard dose Synacthen (ACTH) has been performed for six of the cases, but the diagnosis remains unclear in the remaining two cases (cases 6 and 7). As a consequence, these children, who both received budesonide within the normal dose range, should not have been included in the series.

  We also agree with the commentary by Dr Russel [1] that another reason to exclude case 7 is that the presenting symptoms included hirsutism, hardly a feature of simple adrenal suppression.

  Two children presented acutely with hypoglycaemia, and had subnormal response to ACTH stimulation test. Both were treated with fluticasone 500 mg/day (one had stopped budesonide treatment 4 months earlier). Of the four remaining cases, three were treated with fluticasone 500-1000 mg/day and one was treated with beclomethasone dipropionate 600 mg/day. All had subnormal response to ACTH stimulation test.

  The conclusion from this report is that, especially in children, it is important to step down treatment of inhaled corticosteroids when possible. The report also indicates a greater potency for dose-related adrenal suppression with fluticasone compared with budesonide, in accordance with an earlier meta-analysis [4].

  Bengt Lindberg
  Dept of Pediatrics
  Malmö University Hospital
  AstraZeneca R&D Lund

  Jarl Ingelf
  AstraZeneca R&D Lund

  Lars-Göran Carlsson
  Dept of Pulmonary Medicine
  Malmö University Hospital
  AstraZeneca R&D Lund

  References
  (1) Patel L, Wales JK, Kiberge MS, Massarano AA, Couriel JM and Clayton PE. Symptomatic adrenal insufficiency during inhaled corticosteroid treatment. Arch Dis Child 2001; 85: 330-334.
  (2) Girard FO and R-D. MC. Adrenal Insufficiency. In Pediatric Endocrinology. Bertrand J, Rappaport R and S. PC. (Eds). Baltimore: Williams & Wilkins. 1993: 333-350.
  (3) Wolthers, OD and Honour JW. Hypothalamic-pituitary-adrenal function in children with asthma and rhinitis treated with topical glucocorticosteroids. Clin Exp Allergy 1998; 28(5): 545-550.
  (4) Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Int Med 1999;159(9):941-955

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  Conflict of Interest:
  None declared.

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• Published on: 23 October 2001

  Systemic effects of inhlaed corticosteroids

  • Ranjan Suri, Respiratory Paediatricians
  • Other Contributors:
    • Sheila McKenzie

  Dear Editor

  In the short report by Patel et al,[1] the authors have described symptomatic adrenal insufficiency in eight children with mild to moderately severe asthma. What was the evidence that these children a) had asthma and b) merited treatment with inhaled corticosteroids? Inhaled corticosteroids are potent locally and are almost entirely transformed into inactive metabolites in the liver, so that their sy...

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  Dear Editor

  In the short report by Patel et al,[1] the authors have described symptomatic adrenal insufficiency in eight children with mild to moderately severe asthma. What was the evidence that these children a) had asthma and b) merited treatment with inhaled corticosteroids? Inhaled corticosteroids are potent locally and are almost entirely transformed into inactive metabolites in the liver, so that their systemic bioavailability is almost all due to their absorption by the lungs.[2] The absorption through the lungs depends, among other things, on the degree of airflow limitation, almost certainly reflecting inflammation. The systemic activity of inhaled corticosteroids has been assessed in normal subjects and/or mild asthmatics. More obstructed subjects such as those with moderate to severe asthma have been assumed to handle inhaled corticosteroids in the same way.[3] However, systemic availability of inhaled corticosteroids is substantially less in patients with moderate to severe asthma than in normal subjects.[4,5] Mild asthmatics, who do not need treatment with high dose inhaled corticosteroids,[6] are likely to be more sensitive to the systemic effects of inhaled corticosteroids, and the cases presented in the article may belong to this group.

  Ranjan Suri
  Sheila McKenzie

  Department of Respiratory Paediatrics
  Royal London Hospital
  Whitechapel Road
  Whitechapel
  London E1 1BB

  References
  (1) Patel L, Wales JK, Kibirige MS, et al. Symptomatic adrenal insufficiency during inhaled corticosteroid treatment. Arch Dis Child 2001;85:330-4.
  (2) O'Byrne PM, Pedersen S. Measuring efficacy and safety of different inhaled corticosteroid preparations. J Allergy Clin Immunol 1998;102:879-86.
  (3) Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Intern Med 1999;159:941-55.
  (4) Brutsche MH, Brutsche IC, Munawar M et al. Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study. Lancet 2000;356:556-61.
  (5) Harrison TW, Wisniewski A, Honour J, et al. Comparison of the systemic effects of fluticasone propionate and budesonide given by dry powder inhaler in healthy and asthmatic subjects. Thorax 2001;56:186-91.
  (6) The British Guidelines on Asthma Management, 1995 Review and Position Statement. Thorax 1997;52(suppl 1):S1-S21.

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  Conflict of Interest:
  None declared.

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