CONGENİTAL ADRENAL HYPERPLAZİA Yrd . Doç. Dr. Gülay çiler erdag

1. CONGENİTAL ADRENAL HYPERPLAZİA Yrd. Doç. Dr. Gülay çiler erdag

3. T The adrenal gland consists of: • an outer cortexresponsible for the synthesis of steroids • an inner medullasynthesis catecholamines T T The adrenal cortex consist of three zones: • an outer GLOMERULOSAend product is the mineralocorticoid ALDOSTERONE(regulates sodium balance) • a middle zone FASCICULATAend product is CORTİSOL • an inner zone RETICULARIS synthesis SEX STEROIDS

6. Congenital adrenal hyperplasia(CAH) is one of the causes of adrenal insufficiency in infancy and childhood • CAH is a disorder present at birth characterized by a deficiency in the hormones CORTISOL,ALDOSTERON and the overproduction of ANDROGEN

7. The different types of AGS are inherited as autosomal recessive gene defects • This defect results in the lack of an enzyme needed by the adrenal gland to make cortisol • In response to deficient cortisol the pituitary gland secretes ACTH that stimulates the adrenal gland:HYPERPLASIA

9. The condition affects both females and males • In FEMALE newborn (pseudohermaphroditism), the clitoris is enlarged with the urethral opening at the base:ambigious genitalia-often appearing more male like than female • The internal structures of the reproductive tract (ovaries,uterus and Fallopian tubes) are normal • As she grows older masculinization of some features takes place:deepening of the voice, pubic hair before 2nd birthday ,appereance of facial hair, failur to menstruate at puberty

10. In a MALE newborn: • The infant may appear normal at birth • During the first few months of life the penis enlarges,the scrotum darkens, pubic hair appears and the voice deepens • Affected males may appear to enter puberty as early as 2-3 years of age.At puberty the testes are small and soft • Bone age is advanced; Mental development is usually normal • In BOTH- Height as chidren will be taller but ultimate adult height will be significantly shorter

11. Some forms of CAH are more severe and cause adrenal crisis in the newborn due to SALT WASTING • In the salt losing form of AGS newborns develop symptoms shortly after birth (in the 1st and 2nd week): • Vomiting • Dehydration • Electrolyte changes : • Hyponatremia,hyperkalemia,metabolic acidosis • Cardiac arrythmias • Untreated, this condition can lead to death within 9-14 days after birth • Various types are recognized

13. DEFICIENCY of 21-HYDROXYLASE This enzyme, encoded by CYP21 gene; Defects in CYP21 cause congenital adrenal hyperplasia • Inability to convert 17-hydoxyprogesterone into 11-deoxycortisol and of progesterone to desoxycorticosterone(DOC) • Overproduction of testosterone makes the symptoms • Biochemical diagnostic studies: • Decreased urinary excretion of products of cortisol (17hydroxycorticosteroids ) • Elevated urinary 17 ketosteroids (excretion products of androgen pathway) • Elevated serum testosterone whereas serum cortisol and aldosterone low • Elevated 17-hydoxyprogesterone-by the 3rd day • Elevated urinary pregnanetriol-major urinary metabolite of 17OHP

14. There may be variable allelic forms of this disorder and other individual factors that result in variable expression of the defect both in terms of age at presentation This genetic and clinical heterogenecity has given rise to terms as: CLASSIC-salt wasting, simple virilizing form NONCLASSIC-affected person has a normal phenotype at birth; develop evidence of virilization during later childhood,adolescence or early adulthood ASYMPTOMATIC-no phenotypic features

18. DEFICIENCY of 11-betaHYDROXYLASE • 5-8% of cases • Failure to convert 11deoxycortisol to cortisol • Associated with virilization and usually with hypertension (absent in the first few days of life) • In blood 11deoxycortisol levels are increased • In urine 11deoxycortisol,17KS are increased • Classic-severe • Nonclassic-milder

19. DEFICIENCY of 17 HYDROXYLASE • Males-phenotypic females • Females-failure of sexual development at the expected time • Hypertension- overproduction of DOC • Virilization,amenorrhea • In blood: serum progesteron levels are increased • In urine 17KS,17OH corticoid are decreased

21. PARTIAL or COMPLETE DEFECT in 3BETA HYDROXYSTEROID DEHYDROGENASE ACTIVITY • 5% and less • Failure to convert pregnenolone to progesteron • In male: • incomplete masculinization • Hypospadias • cryptorchidism • In female: • some degree of masculinization • Severe sodium loss occurs • Infant mortality rate is high in complete form • In blood:Pregnenalone levels are increased • In urine -17KS,17OH corticoid levels are decreased

22. CHOLESTEROL DESMOLASE DEFICIENCY • Clinical features are similar to those of 3betahydroxysteroid dehydrogenase deficiency • All steroid excretion is markedly decreased

23. TREATMENT • The goal of treatment is to return the androgen hormone levels to normal • This is achieved by daily administration of dexamethasone,fludrocortisone or hydrocortisone • The gender of a baby with ambigious genitalia is determined by examination of the chromosomes

24. TREATMENT • Reconstrictive surgery for girls with masculine external genitalia is usually performed between the ages of 1-3 • Medication to treat this disorder must be continued for life

25. Prenatal diagnosis is available for some forms of AGS • It is accomplished in the first trimester: • by chorionic villus sampling • in the second trimester: • by measuring hormones such as 17 OHP in the amniotic fluid

26. A newborn screening test is available for the most common form of AGS which can be done on heel stick blood (microfilter paper tecnique to measure 17 0HP • Rapid chromosomal diagnosis should be obtained in NB with ambigious genitalia