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passage of maternal progesterone which exerts partial mineralocorticoid agonistic
activity in the presence of aldosterone defi ciency, which progressively wanes there-
after, as circulating progesterone is metabolized by second week of life. The index
patient was assigned female gender possibly because she had mild genital virilization
(clitoromegaly with posterior labial fusion, Prader stage 2), and further this would
not have been well evident at birth in a premature child. The index child was initiated
with only fl udrocortisone that resulted in resolution of symptoms and correction of
electrolyte abnormalities; however, she failed to grow and continued to become dark.
This is expected because fl udrocortisone supplementation alone does not correct glu-
cocorticoid defi ciency and at recommended doses will not suppress CRH-ACTH
axis, thereby resulting in failure to thrive (as CRH is an anorexigenic peptide) and
progressive darkening of skin. Later, replacement with dexamethasone was initiated
which resulted in clinical improvement but led to decrease in height to 10 th percen-
tile. This is because dexamethasone is 80 times more potent in inhibiting epiphyseal
growth plate activity as compared to hydrocortisone; therefore, hydrocortisone is
preferred in the management of CAH instead of dexamethasone, particularly in
growing children. Hence, in the index case, at 2 years of age, dexamethasone was
substituted with hydrocortisone. Fludrocortisone is to be replaced not only in infants
who present with salt crisis but also in those who have simple virilizing CAH. This
is because infants with CAH, even simple virilizing, do have subclinical aldosterone
defi ciency which results in decreased intravascular volume, thereby leading to
increased ADH secretion, which in turn stimulates ACTH production and conse-
quent worsening of hyperandrogenemia and hyperpigmentation. Increased angioten-
sin II as a result of increased plasma renin activity in these infants also contributes to
growth and proliferation of adrenal cortex. Further, rising level of 17(OH)P exerts
anti-mineralocorticoid activity in the presence of mild aldosterone defi ciency (sim-
ple virilizing CAH). Therefore, supplementation with fl udrocortisone even in simple
virilizing CAH ameliorates all these biochemical abnormalities and reduces the
doses of hydrocortisone. During third year of life, she experienced growth spurt with
appearance of pubic hair accompanied with marked rise in serum 17(OH)P sugges-
tive of GIPP. The dose of hydrocortisone was further increased and it resulted in
decrease in growth velocity, nonprogression of Tanner staging, and suppression of
17(OH)P and testosterone. This indicates overtreatment with glucocorticoids as
serum 17(OH)P was suppressed to 0.5 ng/ml. The recommended target for serum
17(OH)P is to maintain its level between 4 and 12 ng/ml. This cutoff is higher than
the normal reference range, because the dose of glucocorticoid required to suppress
17(OH)P to normal range is higher and detrimental to growth plate, thereby, result-
ing in growth suppression and development of metabolic syndrome. Therefore, the
dose of hydrocortisone was reduced. In addition, monitoring of serum androstenedi-
one and testosterone (in female) may also be useful to guide the therapy. Between the
age 4–7.5 years, serum 17(OH)P continued to remain suppressed, and she experi-
enced another spell of growth spurt along with thelarche (B 3 ). This suggests the onset
of GDPP which was further corroborated by serum LH of 0.3 mIU/ml. The growth
spurt preceded the onset of thelarche, and it is a usual phenomenon during pubertal
development in a growing girl child which was observed in the index patient.
Children with CAH who are either untreated or undertreated experience GIPP, and