Congenital Adrenal Hyperplasia
Presented by: Ahmad Fazwan Junaidi
Adrenal Gland
Adrenal Cortex Hormone Synthesis
In CAH???
There is enzyme deficiency
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 NonclassicMales Females Males Females Males Females
Age at dx Birth-6mo Birth-1mo 2-4 yr Birth-2yr Child to adult
External genitalia
Normal Ambiguous Normal Ambiguous Normal Usually 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 21-OH activity
0 1-2 20-50
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)
17-OHP Basal>20,000 ng/dL Basal> 10,000 – 20,000 ng/dL ACTH stimulated 1,500 – 10,000 ng/dL
Classic salt wasting Classic simple virilizing Nonclassic
100,000
10,000
10,000100 1,000 100,000
1,000
100
0
Basal 17-OHP, ng/dL
ACTH
stim
ulat
ed
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/
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