GROWTH SUPPRESSION BY GLUCOCORTICOID THERAPY

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Growth retardation is commonly experienced by children who undergo long-term treatment with glucocorticoids (GC). Whereas most disorders requiring systemic pharmacotherapy (e.g., organ transplantation, inflammatory bowel disease, rheumatoid diseases, severe asthma) are relatively rare, the expanding use of inhaled GC preparations for the treatment of mild-to-moderate asthma has greatly increased the numbers of children chronically exposed to exogenous GC. Consequently, physicians caring for children are likely to encounter GC-treated patients in whom linear growth must be carefully monitored and GC-induced growth failure recognized. This article reviews the pathophysiology of the effects of GC on growth, current information about the endocrinologic effects of inhaled corticosteroid therapy in children with asthma, and preliminary investigations into reversal of GC-induced growth failure with human growth hormone (GH) therapy.

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MECHANISMS OF GROWTH SUPPRESSION BY GLUCOCORTICOIDS

The pathogenesis of growth suppression by GC is complex and multifactorial, involving several steps in the cascade of events leading to linear growth. During childhood, GH is necessary for epiphyseal growth and maturation. Pulsatile, primarily nocturnal release of pituitary GH (Fig. 1)3 occurs under the influence of interwoven hypothalamic stimulation [via growth hormone–releasing hormone (GHRH)] and inhibition (via somatostatin). In late childhood and adolescence, GH secretion is augmented by

EFFECTS OF INHALED CORTICOSTEROIDS ON GROWTH

Inhaled corticosteroids have significantly reduced the incidence of GC toxicity in children with severe asthma who were previously dependent on systemic steroid therapy. For these children, the benefits of reduced oral GC therapy clearly exceed possible risks of IC therapy. Increased appreciation of the primary role of inflammation in the pathophysiology of asthma and concerns about tolerance to the bronchodilation effects of inhaled beta-adrenergic receptor agonists have elevated IC as

DETECTION AND POTENTIAL TREATMENT OF GROWTH FAILURE IN CHILDREN TREATED WITH GLUCOCORTICOIDS

Accurate monitoring of linear growth depends on accurate measurement using a wall-mounted stadiometer and plotting of growth points on the height-versus-age growth curve. Meaningful determination of linear growth rates requires a minimum 3- to 4-month interval between careful measurements. Because of the variable nature of normal childhood growth and the overriding importance of adequate control of underlying illness, therapeutic decisions regarding dosing of GC should probably await 6 months

SUMMARY

Glucocorticoids exert multiple growth-suppressing effects, interfering with endocrine (e.g., endogenous GH secretion) and metabolic (e.g., bone formation, nitrogen retention, collagen formation) processes essential for normal growth. Relatively small oral doses of daily exogenous GC, alternate-day oral GC therapy, and even IC are capable of slowing growth in some children. These growth-inhibiting and catabolic effects of GC can be variably counterbalanced by GH therapy. With regard to linear

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    Address reprint requests to David B. Allen, MD, Professor of Pediatrics, University of Wisconsin Children's Hospital, Department of Pediatrics, 600 Highland Avenue, Madison, WI 53792–4108

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