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Adult Height Following Prepubertal Treatment With Antiandrogen, Aromatase Inhibitor, and Reduced Hydrocortisone in
Deborah P Merke1,2, Ashwini Mallappa1, Megan Parker1
1Department of Pediatrics, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA.
Context:
Height outcome in patients with classic congenital adrenal hyperplasia (CAH) is suboptimal due to glucocorticoid and androgen excess.
Methods:
In an open, randomized, controlled trial, children with classic CAH were randomized to receive a combination regimen of antiandrogen, aromatase inhibitor, reduced hydrocortisone, and fludrocortisone prior to puberty or standard therapy (hydrocortisone, fludrocortisone). Females continued on antiandrogen during puberty. The primary endpoint was adult height.
Results:
Of 62 children randomized, 45 completed the study. Adult height SDS did not differ between the investigational and control groups (-0.34 [0.93] vs -0.60 [0.89], respectively), mean difference 0.26 [95% CI -0.29, 0.82], P = .35), irrespective of midparental height, but was greater than the predicted adult height pretreatment in both groups (P < .001). Growth rate and rate of bone maturation were reduced in the investigational group prior to puberty, despite lower hydrocortisone dose (7.6 [1.5] vs 15.0 [3.6] mg/m2/day, P < .001), and improvement in predicted adult height appeared greater at pubertal onset (P = .049) compared to standard therapy. Antiandrogen treatment during puberty in girls allowed for lower-dose glucocorticoid, and improved height outcome (adult minus midparental height: -0.7 [4.6] vs -5.6 [5.2] cm, mean difference 4.9 [95% CI 0.09, 9.7], P = .046). Those who received GnRHa had lower growth rate (P = .023) and longer years of unchanged bone age (P = .017), regardless of treatment.
Conclusion:
Prepubertal antiandrogen, aromatase inhibitor combination with reduced hydrocortisone improves short-term predicted height for children with CAH but does not result in taller adult stature than those treated with standard therapy, and is not recommended. Females may benefit from antiandrogen treatment during puberty.
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