1. congenital adrenal hyperplasia
DR BADI ALENAZI
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3. Congenital adrenal hyperplasia
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4. Introduction:
The term congenital adrenal hyperplasia include several autosomal recessive disorders, all of which involve a deficiency or relative defect in cortisol , aldosterone synthesis, increase or decrease level of androgen..
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5. The adrenal consists of the outer cortex and the inner medulla
Aldosterone
Epinephrine
Cortisol
Adrenal androgens
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6. Pituitary
Adrenal
CRH
ACTH
Cortisol
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8. Pathophysiology:
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9. cont.. Decreased cortisol biosynthesis
Anorexia
Poor Weight gain
Fatigue
Vomiting
Weakness
Hypoglycemia
Decreased cortisol biosynthesis
Increased adrenal androgen biosynthesis
Virilization
Dehydration
Hyponatremia
Hyperkalemia
Mineralocorticoid biosynthesis
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10. the major Enzymes involved in CAH:
20-22 desmolase
21-Hydroxylase
11-b-Hydroxylase
17-a-Hydroxylase
3-b-Hydroxysteroid dehydrogenese.
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11. Salt loosing crises due to aldosterone deficiency.
Presentation
Salt loosing crises due to aldosterone deficiency.
Ambigous genitalia in male patient.
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12. Labs : Low cortison, aldosteron and androgen levels.
Decrease or absent response to ACTH stimulation test.
Increase plasma renin level
Massive adrenal enlargment by imaging study.
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13. CAH due to 21 hydroxylase deficiency
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14. CAH due to 21 hydroxylase deficiency
Causes more than 90% of CAH.
Result from mutation in CYT P21.
It is charactericed by decrease production of cortison and aldosteron and increase progestron and 17 oh progestrone..
Less severely affected pt can synthesize aldosterone but have elevated levels of androgens: “Simple virilizing disease”.
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15. Phenotypic Spectrum of the Congenital Adrenal Hyperplasias
Salt-losing
Simple virilizing
Non-classical
SPECTRUM
Adolescent/adult
Female
Hirsutism
Irregular menses
Infertility
Newborn Ambiguous genitalia
Salt loss
Failure to thrive
Young child
Premature pubarche
Advanced bone age
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16. cont.. 1) ALDOSTERONE AND CORTISOL DEFICIENCY:
Include progressive weight loss, anorexia, dehydration, weakness, hypotension, hypoglycemia, hypoNa, and hyperkalemia.
These problems typically first develop in affected infants at 2wk of age.
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17. Virilized 46,XX infants with classical salt-losing CAH
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18. Cont.. 3) POSTNATAL ANDROGEN EXCESS:
Untreated children of both sexes develop additional signs of androgen excess after birth.
Rapid somatic growth and accelerated skeletal maturation with premature closure of epiphysis.
Pubic and axillary hair, acne and deep voice may develop. In girls, breast development and menstruation do not occur unless the excessive production of androgens is suppressed by Tx.
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19. Simple Virilizing CAH:
Premature pubic hair/axillary hair
Body odor
Clitormegaly/phallic enlargement
Acne
Advanced bone age
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20. Late-Onset or Non-Classical CAH
Adolescent or young adult females
Hirsutism
Amenorrhea
+/- Clitoromegaly
Acne
Infertility
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21. LABORATORY FINDINGS
Pt with salt-losing disease have hyponatremia, hyperkalemia, acidosis and often hypoglycemia usually 1-2 wk or longer after birth.
17-OH progesterone is high. Measurement is best 30 min after an IV bolus of cosyntropin (ACTH 1-24).
Cortisol level is low.
Androstenedione and testosterone are elevated in affected females.
ACTH is high .
High Renine levels with low levels of aldosterone.
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22. TREATMENT
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23. Treatment: 1) GLUCOCORTICOID REPLACEMENT:
Hydrocortisone mg/m2/day
Prednisone mg/m2/day
Dexamethasone mg/m2/day
- Double or triple doses are indicated during periods of stress.
- Linear growth, weight gain, pubertal development and skeletal maturation must be followed closely.
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24. Cont.. 2) MINERALOCORTICOID REPLACEMENT:
- Pt with salt wasting disease require tx with fludrocortisone.
- Some pt require sodium supplementation in addition to the mineralocorticoid.
- Serum electrolytes should be measured frequently.
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25. Cont.. 3) SURGICAL MANAGEMENT OF AG.
Virilized females usually undergo surgery between 4-12 mo of age.
Sex assignment of infants with intersex conditions is usually based on expected sexual functioning and fertility in adulthood with surgical correction of the external genitals to confirm with the sex assignment.
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26. Pediatric Endocrinologist
Ob/Gyne
Pediatric Endocrinologist
Multi-disciplinary Team
Child
Family
Psychologist/Behavioral Science
Pediatrician
radiologist
Pediatric Urologist/Surgeon
Geneticist
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27. Summary Male female Ambigous genitalia
17 hydroxlase deficiency hydrxylase deficiency
3-beta-H deficiency b-H Deficiency
20-22 desmolase deficiency
Ambigous genitalia
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