13/09/2015 congenital adrenal hyperplasia congenital adrenal hyperplasia dr badi alenazi

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congenital adrenal congenital adrenal hyperplasiahyperplasia

DR BADI ALENAZIDR BADI ALENAZI

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Congenital adrenal Congenital adrenal hyperplasiahyperplasia

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IntroductionIntroduction::

The term congenital adrenal hyperplasia include several The term congenital adrenal hyperplasia include several autosomal recessive disordersautosomal recessive disorders, all of which involve a , all of which involve a deficiency or relative defect deficiency or relative defect in cortisol , aldosterone in cortisol , aldosterone synthesis, increase or decrease level synthesis, increase or decrease level of androgenof androgen.. ..

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The adrenal consists of the outer cortex andthe inner medulla

Aldosterone

Cortisol

Adrenal androgens

Epinephrine

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Pituitary

Adrenal

CRH

ACTH

Cortisol

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PathophysiologyPathophysiology::

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contcont....

Increased adrenal androgen biosynthesis

Mineralocorticoid biosynthesis

Decreased cortisol biosynthesisAnorexia

Poor Weight gainFatigue

VomitingWeakness

Hypoglycemia

Virilization

DehydrationHyponatremiaHyperkalemia

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the major Enzymes involved in the major Enzymes involved in CAHCAH::

20-22 desmolase 20-22 desmolase

21-Hydroxylase21-Hydroxylase

11-b-Hydroxylase11-b-Hydroxylase

17-a-Hydroxylase17-a-Hydroxylase

3-b-H3-b-Hydroxyydroxysteroid steroid dehydrogenese.dehydrogenese.

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PresentationPresentation

Salt loosing crises due to Salt loosing crises due to aldosterone deficiency.aldosterone deficiency.

Ambigous genitalia in male patient.Ambigous genitalia in male patient.

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LabsLabs: :

Low cortison, aldosteron and androgen Low cortison, aldosteron and androgen levels.levels.

Decrease or absent response to ACTH Decrease or absent response to ACTH stimulation test.stimulation test.

Increase plasma renin levelIncrease plasma renin level

Massive adrenal enlargment by imaging Massive adrenal enlargment by imaging study.study.

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CAH due to 21 hydroxylase deficiency

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CAH due to 21 hydroxylase deficiencyCAH due to 21 hydroxylase deficiency

Causes more than 90% of CAH.Causes more than 90% of CAH.

Result from mutation in CYT P21. Result from mutation in CYT P21.

It is charactericed by decrease production of It is charactericed by decrease production of cortison and aldosteron and increase progestron cortison and aldosteron and increase progestron and 17 oh progestrone.and 17 oh progestrone...

Less severely affected pt can synthesize Less severely affected pt can synthesize aldosterone but have elevated levels of aldosterone but have elevated levels of androgens: “Simple virilizing disease”.androgens: “Simple virilizing disease”.

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Phenotypic Spectrum of thePhenotypic Spectrum of theCongenital Adrenal HyperplasiasCongenital Adrenal Hyperplasias

Salt-losing Simple virilizing Non-classical

SPECTRUMSPECTRUMSPECTRUMSPECTRUM

Newborn Ambiguous genitalia Salt loss Failure to thrive

Young childPremature pubarcheAdvanced bone age

Adolescent/adultFemaleHirsutismIrregular mensesInfertility

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contcont....

1) 1) ALDOSTERONE AND CORTISOL DEFICIENCY: ALDOSTERONE AND CORTISOL DEFICIENCY:

Include progressive weight loss, anorexia, Include progressive weight loss, anorexia, dehydration, weakness, hypotension, hypoglycemia, dehydration, weakness, hypotension, hypoglycemia, hypoNa, and hyperkalemia. hypoNa, and hyperkalemia.

These problems typically first develop in affected These problems typically first develop in affected

infants at 2wk of age. infants at 2wk of age.

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Virilized 46,XX infants with classical salt-losing

CAH

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ContCont....

3) 3) POSTNATAL ANDROGEN EXCESS:POSTNATAL ANDROGEN EXCESS:

Untreated children of both sexes develop Untreated children of both sexes develop additional signs of androgen excess after birth.additional signs of androgen excess after birth.

Rapid somatic growth and accelerated skeletal Rapid somatic growth and accelerated skeletal maturation with premature closure of epiphysis.maturation with premature closure of epiphysis.

Pubic and axillary hair, acne and deep voice Pubic and axillary hair, acne and deep voice may develop. In girls, breast development and may develop. In girls, breast development and menstruation do not occur unless the excessive menstruation do not occur unless the excessive production of androgens is suppressed by Tx.production of androgens is suppressed by Tx.

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Premature pubic hair/axillary hair Body odor Clitormegaly/phallic enlargement Acne Advanced bone age

Simple Virilizing CAHSimple Virilizing CAH::

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Late-Onset or Non-Classical CAHLate-Onset or Non-Classical CAH

Adolescent or young adult femalesAdolescent or young adult femalesHirsutismHirsutismAmenorrheaAmenorrhea+/- Clitoromegaly+/- ClitoromegalyAcneAcneInfertilityInfertility

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LABORATORY FINDINGSLABORATORY FINDINGS

Pt with salt-losing disease have Pt with salt-losing disease have hyponatremiahyponatremia,, hyperkalemia, acidosis and often hypoglycemiahyperkalemia, acidosis and often hypoglycemia usually 1-2 usually 1-2 wk or longer after birth.wk or longer after birth.

17-OH progesterone is high. Measurement is best 30 min 17-OH progesterone is high. Measurement is best 30 min after an IV bolus of cosyntropin after an IV bolus of cosyntropin (ACTH 1-24).(ACTH 1-24).

Cortisol level is low.Cortisol level is low.

Androstenedione and testosterone are elevated in affected Androstenedione and testosterone are elevated in affected females.females.ACTH is high .ACTH is high .High Renine levels with low levels of aldosterone.High Renine levels with low levels of aldosterone.

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TREATMENTTREATMENT

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TreatmentTreatment::

1) 1) GLUCOCORTICOID REPLACEMENT:GLUCOCORTICOID REPLACEMENT:

– HydrocortisoneHydrocortisone 8-18 mg/m2/day 8-18 mg/m2/day – PrednisonePrednisone 1.5-4 mg/m2/day 1.5-4 mg/m2/day – DexamethasoneDexamethasone 0.3-0.9 mg/m2/day0.3-0.9 mg/m2/day

- Double or triple doses are indicated during periods of - Double or triple doses are indicated during periods of

stress.stress.

- Linear growth, weight gain, pubertal development and - Linear growth, weight gain, pubertal development and skeletal maturation must be followed closely. skeletal maturation must be followed closely.

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ContCont....2) 2) MINERALOCORTICOID REPLACEMENT:MINERALOCORTICOID REPLACEMENT:

- Pt with salt wasting disease require tx with - Pt with salt wasting disease require tx with fludrocortisone.fludrocortisone.

- - Some pt require sodium supplementation in Some pt require sodium supplementation in

addition to the mineralocorticoid.addition to the mineralocorticoid.

- Serum electrolytes should be measured frequently.- Serum electrolytes should be measured frequently.

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ContCont....

3) 3) SURGICAL MANAGEMENT OF AG.SURGICAL MANAGEMENT OF AG. Virilized females usually undergo surgery Virilized females usually undergo surgery

between 4-12 mo of age.between 4-12 mo of age.

Sex assignment of infants with intersex Sex assignment of infants with intersex conditions is usually based on expected sexual conditions is usually based on expected sexual functioning and fertility in adulthood with surgical functioning and fertility in adulthood with surgical correction of the external genitals to confirm with correction of the external genitals to confirm with the sex assignment.the sex assignment.

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Child

Family

Multi-disciplinary Team

Pediatric Endocrinologist

Pediatric Urologist/Surgeon

Psychologist/Behavioral Science

radiologist

Ob/Gyne

Pediatrician

Geneticist

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SummarySummaryAmbigous genitaliaAmbigous genitalia

Male Male femalefemale

1717 hydroxlase deficiency hydroxlase deficiency 21 21 hydrxylase deficiencyhydrxylase deficiency

33--beta-H deficiency beta-H deficiency 11-b-H 11-b-H DeficiencyDeficiency

20-2220-22 desmolase deficiencydesmolase deficiency