Download Adrenogenital Syndrome

CONGENİTAL ADRENAL HYPERPLAZİA
YRD. DOÇ. DR. GÜLAY ÇILER ERDAG
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
 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
 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
 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
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
 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
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
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
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
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
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
 CHOLESTEROL DESMOLASE DEFICIENCY
 Clinical features are similar to those of
3betahydroxysteroid dehydrogenase deficiency
 All steroid excretion is markedly decreased
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
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
 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
 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