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Glucocorticoids are used in adrenal replacement therapy when
adrenal insufficiency occurs, or as pharmacologic agents. Following
withdrawal of glucocorticoids used for pharmacologic therapy adrenal
insufficiency can persist for months, especially during times of
stress. The only differences among the various glucocorticoids are their
ratio of glucocorticoid to mineralocorticoid activity, their capacity
to bind to various binding proteins, their molar potency, and their
biologic half life. Dexamethasone is commonly used in reducing
increased intracranial pressure and brain edema. Neurosurgical experience
indicates that the optimal doses are 10 to 100 times those that
would thoroughly saturate all available glucocorticoid receptors,
suggesting that this action of dexamethasone may not be mediated
through the glucocorticoid receptor.
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Glucocorticoid replacement therapy is complicated by undesirable
side effects with even minor overtreatment or undertreatment. Pediatric
glucocorticoid replacement therapy is based on the endogenous secretory
rate of cortisol, which may be as low as 6 mg/m2 in
younger children and 9 mg/m2 in older children
and adolescents, but there is considerable variation in the “normal” cortisol
secretory rate among different children of the same size. Several
additional factors must be considered in tailoring a specific child’s
glucocorticoid replacement regimen as discussed below.
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The Cause of
Adrenal Insufficiency
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When treating autoimmune adrenalitis or other forms of Addison
disease, it is prudent to err slightly on the side of undertreatment.
This will eliminate the possibility of glucocorticoid induced
iatrogenic growth retardation and will permit the pituitary to continue
to produce normal to slightly elevated concentrations of corticotropin
(ACTH). This ACTH will continue to stimulate the remaining functional
adrenal steroidogenic machinery and also provide a convenient means
of monitoring therapy. By contrast, when treating severe, virilizing
congenital adrenal hyperplasia, the adrenal should be suppressed
more completely, as essentially all adrenal steroidogenesis will
result in the production of unwanted androgens, with their consequent
virilization and rate of advancement of bony maturation that is
more rapid than the rate of advancement of height. However, overtreatment
will also compromise growth.
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Presence or
Absence of Associated Mineralocorticoid Deficiency
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Children with mild degrees of mineralocorticoid insufficiency
(eg, simple virilizing congenital adrenal hyperplasia [CAH])
may continue to have mildly elevated ACTH values, suggesting insufficient
glucocorticoid replacement in association with elevated plasma renin
activity (PRA). In some children, the ACTH is elevated in response
to chronic, compromised hypovolemia, attempting to stimulate the
adrenal to produce more mineralocorticoid. In such children without
overt signs of mineralocorticoid insufficiency, treatment with mineralocorticoid
replacement may permit one to decrease the amount of glucocorticoid
replacement needed to suppress plasma ACTH. This reduction in glucocorticoid
therapy reduces the likelihood that adult height will be compromised.
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Formulation
of Glucocorticoid Used for Treatment
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Very potent, long acting glucocorticoids, such as dexamethasone
or prednisone, are preferred in the treatment of adults but are
rarely appropriate for replacement therapy in children. As children
are continually growing and changing their ...