congenital adrenal hyperplasia DR BADI ALENAZI 21/04/2017

21/04/2017

Congenital adrenal hyperplasia 21/04/2017

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.. 21/04/2017

The adrenal consists of the outer cortex and the inner medulla Aldosterone Epinephrine Cortisol Adrenal androgens 21/04/2017

Pituitary Adrenal CRH ACTH Cortisol 21/04/2017

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Pathophysiology: 21/04/2017

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 21/04/2017

the major Enzymes involved in CAH: 20-22 desmolase 21-Hydroxylase 11-b-Hydroxylase 17-a-Hydroxylase 3-b-Hydroxysteroid dehydrogenese. 21/04/2017

Salt loosing crises due to aldosterone deficiency. Presentation Salt loosing crises due to aldosterone deficiency. Ambigous genitalia in male patient. 21/04/2017

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. 21/04/2017

CAH due to 21 hydroxylase deficiency 21/04/2017

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”. 21/04/2017

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 21/04/2017

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. 21/04/2017

Virilized 46,XX infants with classical salt-losing CAH 21/04/2017

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. 21/04/2017

Simple Virilizing CAH: Premature pubic hair/axillary hair Body odor Clitormegaly/phallic enlargement Acne Advanced bone age 21/04/2017

Late-Onset or Non-Classical CAH Adolescent or young adult females Hirsutism Amenorrhea +/- Clitoromegaly Acne Infertility 21/04/2017

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. 21/04/2017

TREATMENT 21/04/2017

Treatment: 1) GLUCOCORTICOID REPLACEMENT: Hydrocortisone 8-18 mg/m2/day Prednisone 1.5-4 mg/m2/day Dexamethasone 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. 21/04/2017

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. 21/04/2017

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. 21/04/2017

Pediatric Endocrinologist Ob/Gyne Pediatric Endocrinologist Multi-disciplinary Team Child Family Psychologist/Behavioral Science Pediatrician radiologist Pediatric Urologist/Surgeon Geneticist 21/04/2017

Summary Male female Ambigous genitalia 17 hydroxlase deficiency 21 hydrxylase deficiency 3-beta-H deficiency 11-b-H Deficiency 20-22 desmolase deficiency Ambigous genitalia 21/04/2017