Congenital adrenal hyperplasia (CAH) is a family of inherited disorders affecting the adrenal glands caused by a deficiency in enzymes involved in cortisol and aldosterone production. The most common type (over 90% of cases) is 21-hydroxylase deficiency, which is autosomal recessive and can cause ambiguous genitalia in females and other symptoms. Clinical manifestations include salt wasting, low blood sugar, and excessive male hormone production leading to virilization. Diagnosis involves blood tests to measure hormone levels before and after stimulation with ACTH. Treatment consists of glucocorticoid and mineralocorticoid hormone replacement, monitoring of hormone levels, and surgery to correct ambiguous genitalia.

1. Congenital Adrenal HyperplasiaPresented by: Ahmad FazwanJunaidi

2. Adrenal Gland

3. Adrenal Cortex Hormone Synthesis There is enzyme deficiencyIn CAH???

4. 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

6. Types of CAH1. 21-hydroxylase deficiency (>90%) Classical - salt wasting(75%; 1 in 15,000) - simple virilizing (25%; 1 in 60,000)Nonclassic (1 in 1,000) Others :11Ᏸ-hydroxylase deficiency(3-5 %, 1 in 100,000)

7. 17α-hydroxylase deficiency / C 17 lyase deficiency (1%)

8. 3 Ᏸ-hydroxysteroiddehydrogenase deficiency(1%)CAH due to 21-OH deficiencyPediatrics Endocrinology, Mechanisms, Manifestations and Management, Ora H. Pescovitz, Erica A. Eugster, 2004 by Lippincott Williams & Wilkins.

10. Clinical ManifestationCortisol 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.

11. InvestigationKaryotyping (determine sex chromosome)Abdominal Ultrasound – to detect presence of uterus, cervix and vagina.Serum 17-hydroxyprogesterone

12. DiagnosisBiochemical diagnostic studies: - elevated serum 17-OHP (0.25mg IV bolus of ACTH after 60min)100,00010,000ACTH stimulated1,000100010,0001001,000100,000Basal 17-OHP, ng/dL

13. ManagementGlucocorticoids (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.

14. 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.

15. ComplicationsFemales – suboptimal breast enlargement, late menarche, amenorrhea, irregular menses, *reduced insulin sensitivity, PCOSMales – oligospermia, testicular tumor

16. Adrenal Crisisimportant to recognize because of its potentially life-threatening implicationswhen the adrenal is prevented from producing normal amounts of its vital hormonesSymptoms 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).