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/