2011 PREP SA on CD-ROM
Question: 122
You are seeing a 6-year-old girl for a health supervision visit. On physical examination, you note
Sexual Maturity Rating (SMR) 3 pubic hair and SMR 1 breast tissue. You noted no pubic hair last
year. She has had a growth spurt in the past 2 years and is presently at the 75th percentile for
height (Item Q122). Her weight is at the 50th percentile for age. Her blood pressure is 90/60 mm
Hg. The remainder of her evaluation is within normal parameters except for possible
clitoromegaly. The radiologist interprets a bone age radiograph as 8 years.
Of the following, the MOST helpful diagnostic laboratory blood test is measurement of
A. androstenedione
B. dehydroepiandrosterone sulfate
C. electrolytes
D. 17-hydroxyprogesterone
E. testosterone
Copyright © 2010 by the American Academy of Pediatrics
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2011 PREP SA on CD-ROM
Question: 122
(Courtesy of L Levitsky)
Copyright © 2010 by the American Academy of Pediatrics
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2011 PREP SA on CD-ROM
Critique: 122
Preferred Response: D
The girl described in the vignette has an advanced bone age, rapid growth rate over 2
years, pubic hair, and clitoromegaly. The most likely explanation for these findings in a girl is
congenital adrenal hyperplasia (CAH). Because the degree and the timing of onset of virilization
in children who have CAH depends upon the degree of enzyme activity of the most severely
affected of the two inherited cyp21 genes, there is a spectrum of presentations in this disorder.
The presentations can range from almost complete enzyme deficiency resulting in
masculinization of female fetuses and the rapid development of a salt-losing crisis to very mild
virilization of adult females, which may be confused with polycystic ovary syndrome in adult
women. Within this spectrum, children have been classified as having classic salt-losing CAH,
non-salt-losing, and nonclassic CAH identified at various ages to adulthood.
The incidence of classic CAH in the United States is about 1 in 14,000, but the incidence of
later-onset forms is reported to be 1 in 100 to 1 in 1,000 among whites, in whom it is more
common than other racial groups. Classic CAH most commonly results from 21-hydroxylase
deficiency (95%). More than 70% of children present with a salt-losing crisis within the first
several weeks after birth. Girls who have this condition exhibit masculinization of genital
development at birth (Item C122). Some children can produce enough mineralocorticoid
(aldosterone) (non-salt losers) and, therefore, are identified only because of masculinization of
genital development in baby girls and isosexual precocity in boys. Children who have the classic
form of CAH usually are identified via prenatal screening for 17-hydroxyprogesterone.
The diagnosis of CAH resulting from 21-hydroxylase deficiency (the most common type) is
based on the finding of an elevated 17-hydroxyprogesterone concentration in response to an
adrenocorticotrophic hormone stimulus or in a first morning specimen, when adrenal steroid
release is at its highest. Dehydroepiandrosterone sulfate concentrations are elevated to pubertal
ranges in CAH, but such findings also are seen in children who have premature pubarche.
Although androstenedione may be elevated in children who have CAH, such a finding is not
diagnostic. Because most children have greater elevations in 17-hydroxyprogesterone, the end
product just before the enzymatic block in adrenal biosynthesis, this is taken as the gold
standard for diagnosing 21-hydroxylase deficiency, although evaluation of other steroid
precursors or genetic analysis is necessary for confirmation. Serum electrolyte values are
abnormal in decompensated classic CAH associated with aldosterone deficiency. In this
situation, low serum sodium and elevated serum potassium values might be expected, but
electrolyte abnormalities are not found in late-onset CAH. The testosterone value is somewhat
elevated in late-onset CAH, but this finding is not diagnostic.
Suggested reading:
Antal Z, Zhou P. Congenital adrenal hyperplasia: diagnosis, evaluation and management. Pediatr
Rev. 2009;30:e49-e57. DOI: 10.1542/10.1542/pir.30-7-e49. Available at:
http://pedsinreview.aappublications.org/cgi/content/full/30/7/e49
Armengaud JB, Charkaluk ML, Trivin C, et al. Precocious pubarche: distinguishing late-onset
congenital adrenal hyperplasia from premature adrenarche. J Clin Endocrinol Metab.
Copyright © 2010 by the American Academy of Pediatrics
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2011 PREP SA on CD-ROM
2009;94:2835-2840. Abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/19454583
Niemann LK. Genetics and clinical presentation of nonclassic (late-onset) congenital adrenal
hyperplasia due to 21-hydroxylase deficiency. UpToDate Online 17.3. 2009. Available at:
http://www.uptodateonline.com/online/content/topic.do?topicKey=adrenal/20734&selectedTitle=9
%7E86&source=search_result
Nimkarn S, New MI. 21-hydroxylase-deficient congenital adrenal hyperplasia. GeneReviews.
2009. Available at: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cah
Copyright © 2010 by the American Academy of Pediatrics
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2011 PREP SA on CD-ROM
Critique: 122
(Reprinted with permission from Antal Z, Zhou P. Congenital adrenal hyperplasia: diagnosis,
evaluation and management. Pediatr Rev. 2009;30:e49-e57)
Virilization of the external genitalia of a female infant affected with congenital adrenal hyperplasia
due to 21-hydroxylase deficiency. Note complete fusion of the labioscrotal folds and a male penile
appearance without testes.
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