359- How to treat a child with classical CAH due to 21α-hydroxylase defi ciency?
Children with classical CAH due to 21α-hydroxylase defi ciency should be
treated with hydrocortisone at doses of 10–15 mg/m^2 /day in three divided
doses and fl udrocortisone at doses of 100–200 μg/m^2 /day. In addition, oral
salt (1–2 g/day) should also be administered during early infancy. High-dose
glucocorticoids should be administered in these children during periods of
stress like infection, trauma, or surgery. Genital reconstructive surgery
should be considered at an appropriate age based on the severity of
ambiguity.- Why is hydrocortisone preferred over other glucocorticoids in the management
of CAH in children?
Hydrocortisone is preferred over other glucocorticoids like prednisolone and
dexamethasone as it is physiological, has short duration of action, and exerts
minimal detrimental effects on epiphyseal growth plate. It has been shown that
at equivalent doses (in terms of glucocorticoid activity), prednisolone has
10–15-fold higher and dexamethasone 70–80-fold higher growth inhibitory
effects, as compared to hydrocortisone. However, if the dose of hydrocortisone
exceeds 20 mg/m^2 /day in infants and 15–17 mg/m^2 /day in adolescents, it may
also exert growth-suppressive effects.- What is the rationale of mineralocorticoid therapy in addition to glucocorti-
coids in patients with simple virilizing CAH due to 21α-hydroxylase
defi ciency?
Patients with simple virilizing CAH due to 21α-hydroxylase defi ciency have
1–5 % residual enzymatic activity, which is suffi cient to prevent salt-wasting
crisis. However, these patients have subclinical aldosterone defi ciency as evi-
denced by elevated plasma renin activity (PRA) and predisposition for salt
crisis during stress. Subclinical aldosterone defi ciency results in chronic deple-
tion of sodium and extracellular fl uid volume. This results in activation of
renin–angiotensin axis and consequently increased angiotensin II levels, lead-
ing to increased secretion of ACTH from the pituitary gland via increasing the
secretion of CRH as well as ADH. Angiotensin II is also a potent adrenocorti-
cal growth promoter. In addition, the chronic extracellular volume depletion
also results in increased ADH secretion and further promotes ACTH drive to
adrenal gland. This increased ACTH drive mandates a higher dose of glucocor-
ticoids to normalize adrenal androgens. Hence, therapy with fl udrocortisone
results in lowering of glucocorticoid doses and improves growth potential
(Fig. 10.13 ).10 Congenital Adrenal Hyperplasia