T The adrenal gland consists of: an outer cortex responsible for the synthesis

of steroids an inner medulla synthesis catecholamines

TT

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