Download Congenital adrenal hyperplasia

congenital adrenal
hyperplasia
DR BADI ALENAZI
23/05/2017
objectives
 Pathophysiology of pituitary adrenal axis
 Major enzyme def in CAH
 21 OH CAH symptom and sign
 21 OH CAH type and presentation
 21 OH CAH treatment
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‫أهمية التفريق بين الجنسين في االسالم‬
‫الطهارة – اآلذان‪ -‬الصالة – األمامة – الجماعة اإلعتكاف‬
‫– الحج – التلبية – اإلحرام – العورة – اللباس – الجهاد –‬
‫الخيرية – البلوغ‪ -‬النسب –– الميراث – الوصية – الوقف‬
‫– القصاص – الشهادة – الوالية – الختان – الزواج –‬
‫الطالق – الرضاعة – الغسل – التكفين – الصالة عليه –‬
‫الدفن‬
Congenital adrenal
hyperplasia
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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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The adrenal consists of the outer cortex and
the inner medulla
Aldosterone
Epinephrine
Cortisol
Adrenal androgens
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CRH
Pituitary
ACTH
Cortisol
Adrenal
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Pathophysiology:
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cont..
 Decreased cortisol biosynthesis
 Increased adrenal
androgen biosynthesis
 Mineralocorticoid biosynthesis
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Anorexia
Poor Weight gain
Fatigue
Vomiting
Weakness
Hypoglycemia
Virilization
Dehydration
Hyponatremia
Hyperkalemia
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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Presentation
Salt loosing crises due to aldosterone deficiency.
Ambigous genitalia in male patient.
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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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CAH due to 21 hydroxylase deficiency
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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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Phenotypic Spectrum of the
Congenital Adrenal Hyperplasias
Salt-losing
Simple virilizing
Non-classical
SPECTRUM
Newborn Ambiguous
genitalia
Salt loss
Failure to thrive
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Young child
Premature pubarche
Advanced bone age
Adolescent/adult
Female
Hirsutism
Irregular menses
Infertility
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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Virilized 46,XX infants with
classical salt-losing CAH
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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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Simple Virilizing CAH:
Premature pubic hair/axillary hair
Body odor
Clitormegaly/phallic enlargement
Acne
Advanced bone age
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Late-Onset or Non-Classical CAH
Adolescent or young adult females
Hirsutism
Amenorrhea
+/- Clitoromegaly
Acne
Infertility
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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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TREATMENT
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Treatment:
1) GLUCOCORTICOID REPLACEMENT:
– Hydrocortisone
– Prednisone
– Dexamethasone
8-18 mg/m2/day
1.5-4 mg/m2/day
0.3-0.9 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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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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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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Ob/Gyne
Pediatric Endocrinologist
Multi-disciplinary Team
Psychologist/
Behavioral
Science
Family
Pediatrician
Child
Pediatric Urologist/Surgeon
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radiologist
Geneticist
Summary
Ambigous genitalia
Male
female
17 hydroxlase deficiency
21 hydrxylase deficiency
3-beta-H deficiency
11-b-H Deficiency
20-22 desmolase deficiency
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