351- In a newborn with ambiguous genitalia, what are the possibilities to be consid-
ered when serum 17(OH)P is only mildly elevated?
In a newborn with ambiguous genitalia, if the stimulated serum 17(OH)P is
mildly elevated (10–100 ng/ml), CAH due to causes other than 21α-hydroxylase
defi ciency should be considered. These include 11β-hydoxylase and cyto-
chrome P450-oxidoreductase (POR) defi ciency. The diagnosis of
11 β-hydoxylase can be confi rmed by the estimation of 11-deoxycortisol, and
POR defi ciency by estimation of serum/urinary steroids (pregnenolone, proges-
terone, and 17(OH)P metabolites) with gas chromatography/mass spectros-
copy. Further, genetic analysis can be performed, if required.- What are the causes of elevated serum 17(OH)P other than CAH?
The disorders associated with increased 17(OH)P include polycystic ovarian
disease, adrenocortical carcinoma, and the use of drugs like ketoconazole and
spironolactone.- What is the rationale of neonatal screening for CAH?
The incidence of classical CAH is approximately 1 in 16,000–20,000. Newborn
screening for CAH is recommended as the disease is potentially fatal and mor-
tality rate due to salt-wasting is approximately 4–10 % in the unscreened popula-
tion. Further, CAH can be easily diagnosed by a simple blood test [serum
17(OH)P], and early diagnosis and therapy improves outcome. The greatest ben-
efi t of neonatal screening is prevention of salt-wasting crises, especially in a
male child who may otherwise be missed due to lack of genital ambiguity. This
is evidenced by the female preponderance in studies performed prior to the intro-
duction of neonatal screening program for CAH and advent of equal male to
female ratio, thereafter. In addition, neonatal screening helps in early and appro-
priate gender assignment and allows timely initiation of therapy to prevent pro-
gression of virilization and morbidity associated with surgical intervention.- How to perform neonatal screening for CAH?
Neonatal screening for CAH is performed by estimation of 17(OH)P as a two-
tier procedure; fi rst-tier using immunoassay and second-tier using liquid chro-
matography-tandem mass spectrometry (LC-MS/MS) performed on dried
blood spot on fi lter paper (Guthrie card). The fi rst-line screening test should be
performed on day 3 of life in a term newborn as serum 17(OH)P levels are usu-
ally elevated in neonates during fi rst 2 days of life [neonatal surge of 17(OH)P]
as well as in preterm newborn. If the fi rst-line screening test demonstrates ele-
vated 17(OH)P levels, second-tier test should be employed. Neonates with
elevated 17(OH)P and symptoms or hyponatremia/hyperkalemia should be
considered to have CAH and treated accordingly. However, those neonates with
elevated 17(OH)P who are asymptomatic should be subjected to ACTH10 Congenital Adrenal Hyperplasia