Dexamethasone Therapy of Congenital Adrenal Hyperplasia and the Myth of the “Growth Toxic” Glucocorticoid

Abstract

The use of long-acting glucocorticoids in the treatment of individuals with Congenital Adrenal Hyperplasia (CAH) has been greeted with controversy. Avoidance of dexamethasone therapy is in part due to the mistaken assumptions that dexamethasone is 30-fold more potent than hydrocortisone in suppressing adrenal activity, resulting in the overtreatment and the “growth toxic” label. However, as shown more than 50 years ago, dexamethasone is 80- to 100-fold (or greater) more potent than hydrocortisone in suppressing adrenal androgen production. When children are treated with low doses of dexamethasone once daily in the morning (0.15–0.3 mg/m2/day of dexamethasone versus 10–25 mg/m2/day of hydrocortisone), studies involving infants and children show that normal growth and skeletal maturation can be achieved, along with appropriate suppression of adrenal androgen secretion. Due to its high potency, the potential for overtreatment remains high with dexamethasone. Thus, it is imperative that dexamethasone-treated children be closely monitored.

Severe Salt-Losing 3β-Hydroxysteroid Dehydrogenase Deficiency: Treatment and Outcomes ofHSD3B2c.35G>A Homozygotes

“…A SD group (n ϭ 9; age, 3.7 Ϯ 3.0 y) required glucocorticoid doses comparable to those reported for most salt-wasting CYP21A2-deficient patients (dexamethasone, 0.22 Ϯ 0.07 mg/m 2 /d; hydrocortisone equivalent, 15.4 Ϯ 4.9 mg/m 2 /d) (1,18,19), whereas a HD group (n ϭ 7; age, 5.6 Ϯ 4.0 y) required considerably larger and more variable doses (dexamethasone, 0.54 Ϯ 0.22 mg/m 2 /d; hydrocortisone equivalent, Figure 2). At all timepoints, significant correlations were observed between 17OHPreg and DHEA (r s ϭ 0.73; P Ͻ .0001), ACTH and DHEA (r s ϭ 0.60; P Ͻ .0001), and ACTH and 17OHPreg (r s ϭ 0.80; P Ͻ .0001) among both groups (Figure 1, B and C).…”

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

“…To circumvent this problem we attempted to define the most suitable time to measure hormone levels related to poor disease control, this dependent on time of dose and glucocorticoid formulation. This may be an alternative strategy especially as some clinicians do measure adrenal androgens during other times of the day such as late in the afternoon 30 . Our opinion is that aiming to measure maximal hormone levels is most useful in clinical management, corresponding to evaluation in the early morning for night time prednisone, or late afternoon for morning prednisone or night time dexamethasone.…”

Final height in congenital adrenal hyperplasia: the dilemma of hypercortisolism versus hyperandrogenism

“…Therefore, it seems desirable to avoid higher hydrocortisone doses, mainly in these periods. The use of long--acting glucocorticoids that could efficiently suppress adrenal androgen production presents great potential for overtreatment, and should be considered with extreme caution (30).…”