08/10/2015 congenital adrenal hyperplasia congenital adrenal hyperplasia DR BADI ALENAZI

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 08/10/2015

أهمية التفريق بين الجنسين في الاسلام الطهارة – الآذان- الصلاة – الأمامة – الجماعة الإعتكاف – الحج – التلبية – الإحرام – العورة – اللباس – الجهاد – الخيرية – البلوغ- النسب –– الميراث – الوصية – الوقف – القصاص – الشهادة – الولاية – الختان – الزواج – الطلاق – الرضاعة – الغسل – التكفين – الصلاة عليه – الدفن الطهارة – الآذان- الصلاة – الأمامة – الجماعة الإعتكاف – الحج – التلبية – الإحرام – العورة – اللباس – الجهاد – الخيرية – البلوغ- النسب –– الميراث – الوصية – الوقف – القصاص – الشهادة – الولاية – الختان – الزواج – الطلاق – الرضاعة – الغسل – التكفين – الصلاة عليه – الدفن

08/10/2015 Congenital adrenal hyperplasia

08/10/2015Introduction: 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..

08/10/2015 The adrenal consists of the outer cortex and the inner medulla Aldosterone Cortisol Adrenal androgens Epinephrine

08/10/2015 Pituitary Adrenal CRH ACTH Cortisol

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Pathophysiology:

cont..  Increased adrenal androgen biosynthesis  Mineralocorticoid biosynthesis  Decreased cortisol biosynthesis Anorexia Poor Weight gain Fatigue Vomiting Weakness Hypoglycemia Virilization Dehydration Hyponatremia Hyperkalemia

08/10/2015 the major Enzymes involved in CAH: desmolase 21-Hydroxylase11-b-Hydroxylase17-a-Hydroxylase 3-b-Hydroxysteroid dehydrogenese.

08/10/2015 Presentation Salt loosing crises due to aldosterone deficiency. Ambigous genitalia in male patient.

08/10/2015 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.

08/10/2015 CAH due to 21 hydroxylase deficiency

08/10/2015 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”.

08/10/2015 Phenotypic Spectrum of the Congenital Adrenal Hyperplasias Salt-losingSimple virilizing Non-classical SPECTRUMSPECTRUM Newborn Ambiguous genitalia Salt loss Failure to thrive Young child Premature pubarche Advanced bone age Adolescent/adult Female Hirsutism Irregular menses Infertility

08/10/2015 cont.. 1) ALDOSTERONE AND CORTISOL DEFICIENCY: Include progressive weight loss, anorexia, dehydration, weakness, hypotension, hypoglycemia, hypoNa, and hyperkalemia. Include progressive weight loss, anorexia, dehydration, weakness, hypotension, hypoglycemia, hypoNa, and hyperkalemia. These problems typically first develop in affected infants at 2wk of age. These problems typically first develop in affected infants at 2wk of age.

08/10/2015 Virilized 46,XX infants with classical salt-losing CAH

08/10/2015 Cont.. 3) POSTNATAL ANDROGEN EXCESS: Untreated children of both sexes develop additional signs of androgen excess after birth. 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. 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. 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.

08/10/2015 Premature pubic hair/axillary hair Body odor Clitormegaly/phallic enlargement Acne Advanced bone age Simple Virilizing CAH:

08/10/2015 Late-Onset or Non-Classical CAH Adolescent or young adult females HirsutismAmenorrhea +/- Clitoromegaly AcneInfertility

08/10/2015 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.

08/10/2015 TREATMENT

Treatment: 1) GLUCOCORTICOID REPLACEMENT: –Hydrocortisone8-18 mg/m2/day –Prednisone mg/m2/day –Dexamethasone mg/m2/day - Double or triple doses are indicated during periods of stress. - Double or triple doses are indicated during periods of stress. - Linear growth, weight gain, pubertal development and skeletal maturation must be followed closely. - Linear growth, weight gain, pubertal development and skeletal maturation must be followed closely.

08/10/2015 Cont.. 2) MINERALOCORTICOID REPLACEMENT: - Pt with salt wasting disease require tx with fludrocortisone. - Pt with salt wasting disease require tx with fludrocortisone. - Some pt require sodium supplementation in addition to the mineralocorticoid. - Some pt require sodium supplementation in addition to the mineralocorticoid. - Serum electrolytes should be measured frequently. - Serum electrolytes should be measured frequently.

08/10/2015 Cont.. 3) SURGICAL MANAGEMENT OF AG. Virilized females usually undergo surgery between 4-12 mo of age. 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. 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.

08/10/2015 Child Family Multi-disciplinary Team Pediatric Endocrinologist Pediatric Urologist/Surgeon Psychologist/ Behavioral Science radiologist Ob/Gyne Pediatrician Geneticist

08/10/2015 Summary Ambigous genitalia Male female 17 hydroxlase deficiency 21 hydrxylase deficiency 3-beta-H deficiency 11-b-H Deficiency desmolase deficiency