CONGENITAL ADRNAL CONGENITAL ADRNAL HYPERPLASIAHYPERPLASIA

NNEDU CHARLES OBIDINNEDU CHARLES OBIDI

MEDICAL FACULTYMEDICAL FACULTY

55THTH YEAR YEAR

Congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) refers to any of several (CAH) refers to any of several autosomal recessive diseases autosomal recessive diseases resulting from mutations of resulting from mutations of

genes for enzymes mediating genes for enzymes mediating the biochemical steps of the biochemical steps of

production of cortisol from production of cortisol from cholesterol by the adrenal cholesterol by the adrenal glands (steroidogenesisglands (steroidogenesis

Most of these conditions Most of these conditions involve excessive or deficient involve excessive or deficient

production of sex steroids production of sex steroids and can alter development of and can alter development of

primary or secondary sex primary or secondary sex characteristics in some characteristics in some

affected infants, children, or affected infants, children, or adults.adults.

The symptoms of CAH vary The symptoms of CAH vary depending upon the form of depending upon the form of

CAH and the sex of the CAH and the sex of the patient. Symptoms are patient. Symptoms are

grouped depending on the grouped depending on the deficient hormone of the deficient hormone of the

adrenal gland which include:adrenal gland which include:

Due to low Due to low mineralocorticoids:mineralocorticoids:

vomiting due to salt-wasting vomiting due to salt-wasting leading to dehydration and leading to dehydration and

deathdeath

Due to inadequate androgen:Due to inadequate androgen:functional and average sized functional and average sized

penis in cases involving penis in cases involving extreme virilization (but no extreme virilization (but no

sperm),ambiguous genitalia, sperm),ambiguous genitalia, in some females, such that it in some females, such that it

can be initially difficult to can be initially difficult to determinedetermine

Cortisol is an adrenal steroid Cortisol is an adrenal steroid hormone that is required for hormone that is required for normal endocrine function. normal endocrine function.

Production begins in the Production begins in the second month of fetal life. second month of fetal life.

Poor cortisol production is a Poor cortisol production is a hallmark of most forms of hallmark of most forms of

CAH.CAH.

Inefficient cortisol production Inefficient cortisol production results in rising levels of ACTH, results in rising levels of ACTH,

which in turn induces which in turn induces overgrowth (hyperplasia) and overgrowth (hyperplasia) and

overactivity of the steroid-overactivity of the steroid-producing cells of the adrenal producing cells of the adrenal cortex. The defects causing cortex. The defects causing

adrenal hyperplasia are adrenal hyperplasia are congenital (i.e., present at congenital (i.e., present at

birth).birth).

Cortisol deficiency in CAH is Cortisol deficiency in CAH is usually partial, and not the most usually partial, and not the most serious problem for an affected serious problem for an affected

person. Synthesis of cortisol person. Synthesis of cortisol shares steps with synthesis of shares steps with synthesis of

mineralocorticoids such as mineralocorticoids such as aldosterone, androgens such as aldosterone, androgens such as

testosterone, and estrogens testosterone, and estrogens such as estradiolsuch as estradiol

The resulting excessive or The resulting excessive or deficient production of these deficient production of these three classes of hormones three classes of hormones

produce the most important produce the most important problems for people with CAH. problems for people with CAH.

Specific enzyme deficiencies are Specific enzyme deficiencies are associated with characteristic associated with characteristic

patterns of over- or patterns of over- or underproduction of underproduction of

mineralocorticoids or sex steroid mineralocorticoids or sex steroid

In all its forms, congenital In all its forms, congenital adrenal hyperplasia due to 21-adrenal hyperplasia due to 21-

hydroxylase deficiency accounts hydroxylase deficiency accounts for about 95% of diagnosed for about 95% of diagnosed

cases of CAH. Unless another cases of CAH. Unless another specific enzyme is mentioned, specific enzyme is mentioned,

"CAH" in nearly all contexts "CAH" in nearly all contexts refers to 21-hydroxylase refers to 21-hydroxylase

deficiency. deficiency.

The terms "salt-wasting CAH", and The terms "salt-wasting CAH", and "simple virilizing CAH" usually "simple virilizing CAH" usually

refer to subtypes of this refer to subtypes of this condition.) CAH due to condition.) CAH due to

deficiencies of enzymes other deficiencies of enzymes other than 21-hydroxylase present than 21-hydroxylase present

many of the same management many of the same management challenges as 21-hydroxylase challenges as 21-hydroxylase deficiency, but some involve deficiency, but some involve

mineralocorticoid excess or sex mineralocorticoid excess or sex steroid deficiency.steroid deficiency.

Milder degrees of inefficiency Milder degrees of inefficiency are usually associated with are usually associated with excessive or deficient sex excessive or deficient sex

hormone effects in childhood hormone effects in childhood or adolescence, while the or adolescence, while the

mildest form of CAH mildest form of CAH interferes with ovulation and interferes with ovulation and

fertility in adults.fertility in adults.

....

Treatment of all forms of CAH Treatment of all forms of CAH may include any of:may include any of:supplying enough supplying enough

glucocorticoid to reduce glucocorticoid to reduce hyperplasia and overproduction hyperplasia and overproduction

of androgens of of androgens of mineralocorticoidsmineralocorticoids

providing replacement providing replacement mineralocorticoid and extra salt mineralocorticoid and extra salt

if the person is deficientif the person is deficient

providing replacement providing replacement testosterone or estrogen at testosterone or estrogen at

puberty if the person is puberty if the person is deficientdeficient

additional treatments to additional treatments to optimize growth by delaying optimize growth by delaying

puberty or delaying bone puberty or delaying bone maturationmaturation

One of our One of our patient patient’s’s

Complaints :anorexia,weight loss, Complaints :anorexia,weight loss, weakness, vomitingweakness, vomitingAnamnesis morbi: child has been ill Anamnesis morbi: child has been ill since birth with poor weight till 2weeks since birth with poor weight till 2weeks of age.At age of 2weeks,he refused of age.At age of 2weeks,he refused eating accompanied by eating accompanied by weakness,vomitting and was then weakness,vomitting and was then hospitalizedhospitalized

InvestigationsInvestigations

►Neurological status: Neurological status: muscle distonia with muscle distonia with moderately moderately decreased motor decreased motor activity with activity with decreased reflexesdecreased reflexes

► Ultrasound Ultrasound investigation:perivainvestigation:perivascular ischaemia of scular ischaemia of brain ,kidneys were brain ,kidneys were normal,uterus was normal,uterus was also visualizes with also visualizes with normal normal status,hypertrophy status,hypertrophy of adrenal gland of of adrenal gland of 22ndnd degree. degree.

Organic acid analysisOrganic acid analysis

Increased ketoacid of 7.5(5.0 – 7.0)Increased ketoacid of 7.5(5.0 – 7.0)

Increase fumaric acid,increased glutaric Increase fumaric acid,increased glutaric acid,increase d-malic acid with acid,increase d-malic acid with

increased oxoproline and citric acid.increased oxoproline and citric acid.

Biochemical AnalysisBiochemical Analysis

►Blood: total cholesterin 5.89(2.95-Blood: total cholesterin 5.89(2.95-5.23mmol),Triglyceride 1.61(0.34-5.23mmol),Triglyceride 1.61(0.34-1.19mmol/l),17 OH hydroxy 1.19mmol/l),17 OH hydroxy progesterone.progesterone.

►Urine:ph 7.0, chloride 1(3-15g/l),Urine:ph 7.0, chloride 1(3-15g/l),

Liver analysis: parenchymatous Liver analysis: parenchymatous enlargement by 3cm with toxic enlargement by 3cm with toxic

cholestatic infiltration in cholestatic infiltration in gallbladder which is also gallbladder which is also

enlarged by 2cm.enlarged by 2cm.Kidney analysis:hyperplasia of Kidney analysis:hyperplasia of kidney parenchyma,moderate kidney parenchyma,moderate

pyeloectasiapyeloectasia

heart: vessels are fine but heart: vessels are fine but with dilation of right with dilation of right

heart .Brain :has evidence of heart .Brain :has evidence of hydrocephalushydrocephalus

DIAGNOSISDIAGNOSIS

► Initial diagnosis:inborn adrenal Initial diagnosis:inborn adrenal dysplasia&dysfunction(by an dysplasia&dysfunction(by an endocrinologist),bilateral cryptorchism endocrinologist),bilateral cryptorchism with sterile disorders,adrenogenital with sterile disorders,adrenogenital syndrome and pylorospasm,intenstinal syndrome and pylorospasm,intenstinal pareses of first type , hypospadia.pareses of first type , hypospadia.

►Conclusive diagnosis : hypertrophy of Conclusive diagnosis : hypertrophy of adrenal gland and genital anomaly.adrenal gland and genital anomaly.

TreatmentTreatment

►Ubixinon:1/4 of tablet everydayUbixinon:1/4 of tablet everyday►Cudesan:Cudesan:►Folic acid:1mg/day for 20daysFolic acid:1mg/day for 20days►Medobiolin:1tab/day for 1monthMedobiolin:1tab/day for 1month►Cardonate:1/2 of tab/day for a monthCardonate:1/2 of tab/day for a month►Analysis control of blood electrolyte , Analysis control of blood electrolyte ,

urinalysis and examination follow upurinalysis and examination follow up

Thank you for your attentionThank you for your attention