367range suggests overtreatment with GnRH agonists. This is because prepuber-
tal gonads produce minor quantities of gonadal steroids, which promotes
GH-dependent IGF1 generation. In addition, coexisting disorders like hypo-
thyroidism and celiac disease should also be considered.- Are there any alterations in adrenomedullary function in children with CAH
due to 21α-hydroxylase defi ciency?
Although the embryological origin of adrenal cortex (mesonephros) and
medulla (neural crest) are different, paracrine actions of cortisol is essential for
normal development and function of adrenal medulla. Cortisol not only main-
tains the integrity of chromaffi n cells in adrenal medulla but also potentiates the
activity of the enzyme phenyl-N-methyl transferase, which catalyzes the con-
version of norepinephrine to epinephrine. Exogenous glucocorticoid adminis-
tration does not improve the adrenomedullary dysfunction as high intra-adrenal
levels of cortisol are required for normal adrenomedullary function, and this
cannot be achieved with exogenous glucocorticoid therapy. The clinical impli-
cation of adrenomedullary dysfunction in patients with CAH due to
21 α-hydroxylase defi ciency include propensity to develop hypoglycemia and
severe hypotension.- What are the medical options available in diffi cult to manage CAH?
In a child with diffi cult to treat CAH, various therapeutic strategies have been
employed. These include administration of higher doses of hydrocortisone (15–
20 mg/m^2 /day), higher dose of hydrocortisone at night (reverse circadian regi-
men), and combination of hydrocortisone along with prednisolone and/or
dexamethasone (basal–bolus). The use of supraphysiological doses of hydro-
cortisone results in adverse effects particularly reduced growth velocity, insulin
resistance, and osteoporosis. Administration of hydrocortisone in reverse circa-
dian regimen has not yielded any benefi cial effects. Combination of hydrocor-
tisone (in divided doses) and prednisolone/dexamethasone (at bedtime) has
been tried; however, limited data is available regarding the effi cacy and safety
of these regimens. Slow-release preparations of hydrocortisone (e.g.,
Chronocort) and continuous subcutaneous hydrocortisone infusion (CSHI) via
pump have been tried in children with diffi cult to control CAH and shown to be
effective. Abiraterone acetate is an oral 17α-hydroxylase inhibitor which has
been shown to be effective in reducing the androgens levels, when added to the
glucocorticoid regimen. In addition, its use is also associated with reduction in
doses of glucocorticoids. There is limited data regarding the use of antiandro-
gens like fl utamide (androgen receptor antagonist) or fi nasteride (5α-reductase
inhibitor) in patients with CAH.10 Congenital Adrenal Hyperplasia