Side effects of steroids revisited☆☆☆
Article Outline
See related articles, p. 21 and p. 25.
The childhood phase of growth is predominantly growth hormone–modulated. However, the impact of adrenarche, which is responsible for the mid-childhood growth spurt, has never been analyzed, least of all in terms of final height. It is common in clinical pediatric practice to observe poor growth in asthmatic children at this time, and there has always been a suspicion that, despite reassurance to the contrary,1 asthma must take its toll. The huge database of Norjavaara et al2 confirms this suspicion to be correct. It is not surprising that the worse the asthma, the worse was the outcome and, because adrenal androgens can be stimulated by corticotropin and suppressed by dexamethasone, steroid medication would, of course, make a bad situation worse.
The investigation of the effects of such treatment on adrenal function is difficult because we are working at the margins of the sensitivity and specificity of tests of minor degrees of adrenal suppression. Low-dose corticotropin testing reveals mild adrenal suppression in a quarter of children receiving very moderate doses of inhaled steroids.3 Growth followed the same pattern.
Nobody died of being short, and asthma is a dangerous disease. No physician should withhold steroids from asthmatic children who need them, but they need to be aware of the consequences. In this respect, data on adrenal function in a very different setting are pertinent.
Felner et al4 examined adrenal function in children with leukemia after high-dose dexamethasone induction therapy had been abruptly stopped after 28 days. They used a cruder version of the corticotropin test than the Finnish authors3 so, as they admit, may have missed minor degrees of adrenal dysfunction. Neither the adrenal suppression nor the variable rate of recovery should surprise us. What is important is the effect it may have had on post-treatment morbidity.
Half of the children with leukemia were readmitted to the hospital with episodes of febrile neutropenia after initial induction therapy had been completed. This is in accord with the clinical experience of colleagues in oncology, but the hospitalized children included all of the adrenal-compromised children and only 2 of the 7 recovered patients. That this difference did not achieve statistical significance in such a small study should not divert our attention from the implication of the observation.
Felner et al4 propose a gradual withdrawal of steroid therapy rather than abrupt discontinuation of treatment. It seems to this observer that a large multicenter, prospective, double-blind, randomized control trial to address this critical issue is overdue. In the meantime, oncologists (and others who prescribe steroids in large doses) need to consider adrenal suppression as a cause of nausea and vomiting when they see patients with fever and neutropenia, which may well be due to cortisol deficiency.
Physicians who prescribe steroids might start by measuring plasma cortisol concentrations in affected patients and might also consider the use of hydrocortisone replacement in addition to their other supportive regimens. Induction regimens for leukemia in Europe currently use doses of dexamethasone with tapering over a week. From the time course of recovery of adrenal function in the patients described by Felner et al,4 this will not be sufficient to obviate the problem.
References
- . Growth and childhood asthma. Arch Dis Child. 1986;61:1049–1055
- . Reduced height in Swedish men with asthma at the age of conscription for military service. J Pediatr. 2000;137:25–29
- . Adrenal suppression, evaluated by a low dose adrenocorticotrophin test, and growth in asthmatic children treated with inhaled steroids. J Clin Endocrinol Metab. 2000;85:652–657
- . Time course of recovery of adrenal function in children treated for leukemia. J Pediatr. 2000;137:21–24
☆ Reprint requests: Charles G. D. Brook, The Middlesex Hospital, Mortimer St, London W1N 8AA, United Kingdom.
☆☆ J Pediatr 2000;137:3-4.
PII: S0022-3476(00)03738-0
© 2000 Mosby, Inc. All rights reserved.
Refers to article:
- Time course of recovery of adrenal function in children treated for leukemia
- Reduced height in Swedish men with asthma at the age of conscription for military service
