Congenital Adrenal

Hyperplasia

Presented by: Ahmad Fazwan Junaidi

Adrenal Gland
 Adrenal Cortex Hormone Synthesis

There is
enzyme
deficiency

In CAH???
What is Congenital Adrenal Hyperplasia (CAH)?

• Congenital Adrenal Hyperplasia (CAH) is a family of inherited

disorders affecting the adrenal glands.
• Autosomal recessive (mutation of chromosome 6 21-
hydroxylase enzyme impairment)
• Commoner in consanguineous marriage
 Types of CAH
1. 21-hydroxylase deficiency (>90%)
 Classical - salt wasting(75%; 1 in 15,000)
- simple virilizing (25%; 1 in 60,000)
 Nonclassic (1 in 1,000)
2. Others :
 11Ᏸ-hydroxylase deficiency(3-5 %, 1 in 100,000)
 17α-hydroxylase deficiency / C 17 lyase deficiency (1%)
 3 Ᏸ-hydroxysteroid dehydrogenase deficiency(1%)
 CAH due to 21-OH deficiency
Classic salt wasting Classic simple virilizing Nonclassic
Males Females Males Females Males Females

Age at dx Birth-6mo Birth-1mo 2-4 yr Birth-2yr Child to adult

External Normal Ambiguous Normal Ambiguous Normal Usually

genitalia normal; may
have
clitoromegaly
Aldosterone Low Normal Normal

Cortisol Low Low Normal

17-OHP Basal>20,000 ng/dL Basal> 10,000 – 20,000 ng/dL ACTH stimulated 1,500 –
10,000 ng/dL
% of normal 0 1-2 20-50
21-OH activity

Pediatrics Endocrinology, Mechanisms, Manifestations and Management, Ora

H. Pescovitz, Erica A. Eugster, 2004 by Lippincott Williams & Wilkins.
 Clinical Manifestation
• Cortisol deficiency – hypoglycemia, inability to withstand
stress, vasomotor collapse, hyperpigmentation, apneic
spells, muscle weakness & fatigue.
• Aldosterone deficiency – hyponatremia, hyperkalemia,
vomiting, urinary sodium wasting, salt craving, acidosis,
failure to thrive, volume depletion, hypotension,
dehydration, shock, diarrhea.
• Androgen excess – ambiguous genitalia, virilization of
external genitalia , hirsutism, early appearance of pubic
hair, penile enlargement , excessive height gain and
skeletal advance.
*Late onset CAH – normal genitalia, have acne, hirsutism,
irregular menses/amenorrhea.
 Investigation
• Karyotyping (determine sex chromosome)
• Abdominal Ultrasound – to detect presence of
uterus, cervix and vagina.
• Serum 17-hydroxyprogesterone
 Diagnosis
• Biochemical diagnostic studies:
- elevated serum 17-OHP (0.25mg IV bolus of ACTH after 60min)
100,000

10,000
ACTH stimulated

1,000

100

0
100 1,000 10,000 100,000
Basal 17-OHP, ng/dL

Classic salt wasting Classic simple virilizing Nonclassic

17-OHP Basal>20,000 ng/dL Basal> 10,000 – 20,000 ng/dL ACTH stimulated 1,500 –
10,000 ng/dL
 Management
• Glucocorticoids (oral hydrocortisone etc.) 13-18 mg/m²/24hr in 3 divided
doses.
Monitoring: serum concentration of adrenal precursors (17-OHP) & linear
growth and skeletal age assessment.

*During stressful state ie febrile ilnesses or surgery, 3x higher dose.

*In severe emergency: intramuscular SC glucocorticoid (Solu-Cortef)

• Mineralocorticoid therapy (fludrocortisone) at a dose of 0.1-0.2 mg/24hr +

sodium chloride supplement 1-2g daily.
Monitoring: serum sodium & potassium, plasma renin activity levels.

• Surgical correction of ambiguous genitalia by 1-2 y/o  normal

development of gender identity.
• CYP21 genotyping can be performed in a
family with history of CAH.
• Treatment with dexamethasone to suppress
fetal ACTH-induced androgen production can
reduce/eliminate ambiguity of external
genitalia in affected female fetuses.
 Complications
• Females – suboptimal breast enlargement,
late menarche, amenorrhea, irregular menses,
*reduced insulin sensitivity, PCOS

• Males – oligospermia, testicular tumor

 Adrenal Crisis
• important to recognize because of its potentially life-threatening
implications
• when the adrenal is prevented from producing normal amounts of
its vital hormones
• Symptoms and signs of adrenal crisis are varied and nonspecific.
• In infancy these include lethargy, vomiting, poor appetite and
failure to thrive.
• In older children chronic fatigue, headache, gastrointestinal
symptoms, salt-craving and excess skin pigmentation may be noted.
• the underlying problems include low blood sugar, low blood
sodium, dehydration, low blood pressure, all predisposing the
individual to heart failure and shock (collapse).
 References
• Nelson Essentials of Paediatrics, 5th ed, 2006,
Elsevier Inc.
• Illustrated Textbook of Paediatrics, 3rd ed, Tom
Lissauer, Graham Clayden, 2007,Elsevier Limited.
• Pediatrics Endocrinology, Mechanisms,
Manifestations and Management, Ora H.
Pescovitz, Erica A. Eugster, 2004 by Lippincott
Williams & Wilkins.
• http://www.caresfoundation.org/
• http://www.aafp.org/