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PEDIATRICS Vol. 112 No. 6 December 2003, pp. 1464-1465

Inhaled Corticosteroids and Urinary Free Cortisol

Lydia Pescollderungg
Diego Giampietro Peroni*
Angelo Pietrobelli*
Giorgio Radetti, MD

Department of Pediatrics
Regional Hospital of Bolzano
39100 Bolzano, Italy
* Pediatric Department
University of Verona
Istituto Pio XII
Misurina 32040, Italy

To the Editor.

Assessment of urinary free cortisol (UFC) is frequently used by pediatric and adult pulmonologists to evaluate the adrenal suppressive effect of inhaled corticosteroids (ICSs).1 However, UFC is a valuable tool in conditions of cortisol excess, but not when hypocorticism is suspected.2 This is related to the lack of sensitivity of the method at low cortisol levels and because low cortisol excretion is often found in normal subjects.1 To verify whether this problem inherent to UFC assessment also applies to the pediatric age, we evaluated the adrenal function of 30 asthmatic children before and after 3 months of treatment with ICS3; 14 children were receiving fluticasone propionate 100 µg twice a day and 16 budesonide 200 µg twice a day. Adrenal function was evaluated by means of a corticotropin-releasing hormone (CRH) test, and UFC assessment and the results were compared. Cortisol was assayed with the Immulite 2000 Cortisol kit (DPC, Los Angeles, CA), which has a sensitivity of 0.20 µg/dL with an intraassay coefficient of variation of 7.2%. A cortisol peak of <180 ng/mL after CRH stimulation was considered as a sign of adrenal suppression, as well as a UFC of <5 µg/24 hours.

No correlation was found between basal and peak of cortisol after CRH and UFC, both before and after therapy. Moreover, in 3 of the 4 patients with subnormal peak cortisol response, there was also a reduction in the 24-hour UFC, which was, however, within the observed range of our study population. In the fourth one, no UFC changes were observed after treatment, thus confirming the lack of specificity and poor precision of UFC at low concentration. These results agree with those of a recent article,4 where it was shown that the determination of UFC after ICS is too dependent on the assay methods and protocols for urine collection. Therefore, UFC does seem to be also in children an unreliable surrogate marker of adrenal suppression and thus should not be used by pediatricians to evaluate the hypothalamic-pituitary axis in subjects treated with ICSs.

REFERENCES

  1. Chrousos GP, Harris AG. Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 1. General principles. Neuroimmunomodulation.1998; 5 :277 –287[CrossRef][ISI][Medline]
  2. Orth DN, Kovacs WJ. The adrenal cortex. In: Wilson JD, Foster DW, Kronemberg HM, Larsen PR, eds. Williams Textbook of Endocrinology. Philadelphia, PA: WB Saunders Co; 1998
  3. Pescollderungg L, Radetti G, Gottardi E, Peroni D, Pietrobelli A, Boner A. Systemic activity of inhaled corticosteroid treatment in asthmatic children: corticotropin releasing hormone test. Thorax.2003; 58 :227 –230[Abstract/Free Full Text]
  4. Fink RS, Pierre LN, Daley-Yates PT, Richards DH, Gibson A, Honour JW. Hypothalamic-pituitary-adrenal axis function after inhaled corticosteroids: unreliability of urinary free cortisol estimation. J Clin Endocrinol Metab.2002; 87 :4541 –4546[Abstract/Free Full Text]

PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics




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