369- When to treat a patient with non-classical CAH due to 21α-hydroxylase
defi ciency?
Children with NCCAH having early pubarche and advanced bone age (>2.5 SD
over chronological age) should be treated with glucocorticoids. However, therapy
should only be continued till the peripubertal age to avoid the untoward conse-
quences of glucocorticoids. Adolescent females with NCCAH who have hirsut-
ism/acne and menstrual irregularity may require short-term glucocorticoid
treatment. However, therapy with oral contraceptives and/or antiandrogens are
equally/more effective. Adult women with NCCAH who have menstrual irregu-
larities and features of virilization can be treated with oral contraceptives and/or
antiandrogens. However, if fertility is a concern, short-term therapy with gluco-
corticoids is indicated to suppress adrenal androgens as well as to target serum
progesterone to <0.6 ng/ml. The preferred glucocorticoid in this scenario is dexa-
methasone administered at bedtime (0.25 mg to 0.5 mg/day). Males with NCCAH
who have TART and/or infertility should be treated with glucocorticoids.- What are the causes of infertility in CAH?
Women with CAH have impaired fertility due to chronic anovulation as a con-
sequence of hyperandrogenemia, secondary polycystic ovarian disease, and
high levels of circulating progesterone. In addition, inadequate introitus, hostile
cervical mucus (as consequence of progesterone excess), and reduced sexual
activity also contribute. In men, infertility may be due to suppression of gonad-
otropins as a result of elevated adrenal androgens or due to the presence of
testicular adrenal rest tumors.- What are the hypertensive variants of CAH?
21 α-hydroxylase defi ciency is the most common cause of CAH and is associated
with salt-wasting crisis in approximately three-fourth of patients with classical
CAH. However, CAH due to 11β-hydoxylase and 17α-hydroxylase enzyme defi -
ciencies are associated with hypertension. Defi ciency of the enzyme
11 β-hydoxylase results in accumulation of deoxycorticosterone acetate (DOCA).
Although DOCA is a weak mineralocorticoid, high concentration of DOCA in
patients with 11β-hydoxylase defi ciency results in hypertension and hypokalemia.
Defi ciency of the enzyme 17α-hydroxylase results in hypertension and hypokale-
mia due to diversion of precursor metabolites (pregnenolone and progesterone) to
mineralocorticoid synthetic pathway, resulting in higher levels of DOCA. However,
plasma aldosterone level is low, due to DOCA- mediated inhibition of RAAS and
consequent decrease in angiotensin II which downregulates aldosterone synthase
(CYP11B2). Finally, overtreatment with glucocorticoids and mineralocorticoids
is also a common cause of hypertension in patients with CAH.10 Congenital Adrenal Hyperplasia