This presentation I made for my peadiatric seminar with help of all the available sources .I hope this will be useful for you guys too.

1. CONGENITAL ADRENAL
HYPERPLASIA
DR.SOUMYA KORI
INTERN(2014)

2. ADRENAL GLAND
• PRODUCTION OF HORMONES BEGINS IN
EMBRYONIC STAGES OF LIFE BY 7 WEEKS OF
GESTATION.
• ALL ADRENO-CORTICAL HORMONES ARE
STEROID COMPOUNDS ,DERIVED FROM
CHOLESTEROL (CIRCULATING LDH)
• ADRENAL MEDULLA –RELEASE OF EPINEPHRINE
AND SOME AMOUNTS OF NOREPINEPHRINE.

3. CONGENITAL ADRENAL
HYPERPLASIAS (CAH)
1.A GROUP OF HERITABLE DISORDERS
ASSOCIATED WITH AN INABILITY /REDUCED
ABILITY TO PRODUCE CORTISOL.
2.THE DISEASE BEGINS EARLY IN GESTATION AND
LEADS TO DISEASE THAT MANIFEST AT BIRTH/
LATER.
WITHOUT CORTISOL THERE IS NO NEGATIVE
FEEDBACK DUE TO THIS THERE IS EXCESSIVE
SECRETION OF CRH FROM HYPOTHALAMUS &
ACTH FROM ANTERIOR PITUITARY.

4. • CONTINUED SECRETION OF ACTH CAUSES
UNREMITTING STIMULATION OF THE ADRENAL
CORTEX, LEADING TO HYPERPLASIA.
• IN MOST CASES, ADRENAL HYPERPLASIA ALSO
INVOLVES A DEFICIENCY IN ALDOSTERONE,
WHICH RESULTS IN MILD TO SEVERE LOSS OF
BODY SODIUM.
• IN SOME, IT ALSO INVOLVES OVERPRODUCTION
OF ADRENAL ANDROGENS, WHICH, IN AFFECTED
FEMALES, RESULTS IN PRENATAL VIRILIZATION
WITH AN AMBIGUOUS /MALE EXTERNAL
GENITALIA AT BIRTH.

5. • CLASSIFICATION:
• 1)21-HYDROXYLASE DEFICIENCY (MOST
COMMON)
• 2)11Β-HYDROXYLASE DEFICIENCY
• 3)3Β-HSD DEFICIENCY
• 4)17-HYDROXYLASE DEFICIENCY
• 5)LIPOID CAH

6. CAH DUE TO 21-HYDROXYLASE
DEFICIENCY
• 95% OF THE CASES OF CAH ARE THE
RESULT OF DEFICIENCY IN THE
ENZYME STEROID 21-
HYDROXYLASE. ABSOLUTE OR
PARTIAL DEFICIENCY IN THIS
ENZYME LEADS TO TWO PROBLEMS:
1. DEFICIENCY IN PRODUCTION OF
CORTISOL AND ALDOSTERONE
2. SHUNTING OF STEROID
PRECURSORS TO FORM

8. • 21-HYDROXYLASE DEFICIENCY
• ◦ACCOUNTS FOR 95% OF ALL CASES.
• ◦CLASSIC TYPE
• 1)SALT WASTING FORM
• 2)SIMPLE VIRILIZING FORM
• ◦NON-CLASSIC TYPE

9. • ◦ CLASSIC
• 1) SW FORM : 75%
• ◦ MOST LETHAL FORM OF 21 HYDROXYLASE DEFICIENCY
• ◦ MANIFESTS AS SALT WATER CRISIS AT 2 TO 6 WEEKS OF LIFE.
• ◦ FEATURES :
• ◦ VOMITING
• ◦ PIGMENTATION
• ◦ ABNORMAL GENITAL APPEARANCE
• ◦ LETHARGY
• ◦ FTT
• ◦ SHOCK WITH ↓ED URINE OUTPUT.

10. • BIOCHEMICAL FINDINGS :
• ◦ HYPONATREMIA
• ◦ HYPERKALEMIA
• ◦ HYPOGLYCEMIA
• ◦ METABOLIC ACIDOSIS
• ◦ HEMOCONCENTRATION.

11. • ◦ A: FEMALE INFANTS PRESENT AT BIRTH WITH
• AMBIGUOUS GENITALIA AS A RESULT OF IN
• UTERO EXPOSURE TO ANDROGENS.
• ◦ A: FEMALE INFANTS PRESENT AT BIRTH WITH
• AMBIGUOUS GENITALIA AS A RESULT OF IN
• UTERO EXPOSURE TO ANDROGENS.
◦ A: Female infants
present at birth with
ambiguous genitalia as a
result of in
utero exposure to
androgens.

12. •2) SV FORM :25%
• THESE HAVE MILDER DEFECT WITH
MINERALOCORTICOID SECRETION SUFFICIENT TO
PREVENT SW .
• ◦ FEATURES :
• ◦ GIRLS PRESENT WITH GENITAL AMBIGUITY ,
SOMETIMES VIRILISED TO THE EXTENT OF BEING
REARED AS BOYS AND MANIFESTS WITH CYCLICAL
HAEMATURIA DURING ADOLESCENCE.
• ◦ BOYS HAVE PERIPHERAL PRECOCIOUS PUBERTY,
USUALLY DIAGNOSED VERY LATE WITH
SIGNIFICANT BONE AGE ADVANCEMENT AND
COMPROMISED FINAL HEIGHT.

13. •NON-CLASSIC TYPE
• ◦ PRODUCE NORMAL AMOUNTS OF CORTISOL AND
ALDOSTERONE AT THE EXPENSE OF MILD-TO-
MODERATE OVERPRODUCTION OF SEX HORMONE
PRECURSORS.
• AT PRESENTATION
• ◦ HIRSUTISM(MOST COMMON) SYMPTOM IN
APPROXIMATELY 60 PERCENT OF SYMPTOMATIC
WOMEN,
• ◦ OLIGOMENORRHEA (54 %)
• ◦ ACNE (33 %).
• ◦ DECREASED FERTILITY IS AN INDICATION FOR

14. • OTHER FORMS OF CAH
FIVE GENETIC MUTATIONS IN THE CORTISOL BIOSYNTHESIS
PATHWAY:
• -FOUR GENES ( CYP21 , CYP17, CYP 11B1, HSD3B2 )
THAT ENCODE ENZYMES FOR STEROID HORMONE
SYNTHESIS
• -ONE GENE ( STAR ) THAT ENCODES THE INTRACELLULAR
CHOLESTEROL TRANSPORT PROTEIN, CAN CAUSE CAH.
• ◦ AUTOSOMAL RECESSIVE INHERITANCE
• ◦ ONLY 21OHD AND 11-BETA HYDROXYLASE DEFICIENCY
ARE PREDOMINANTLY VIRILIZING DISORDERS.
• ◦ PATIENTS WHO HAVE THE REMAINING DISORDERS HAVE
IMPAIRED PRODUCTION OF BOTH CORTISOL BY THE
ADRENALS AND GONADAL STEROIDS.
• ◦ MALE PATIENTS EXHIBIT VARYING DEGREES OF
UNDERVIRILIZATION CAUSED BY DEFICIENT

15. CAH: DIAGNOSIS AND PRENATAL
SCREENING
• 21-HYDROXYLASE DEFICIENCY IS FIRST
SUSPECTED IN A NEWBORN INFANT WITH
"AMBIGUOUS GENITALIA".
• ELEVATED BLOOD LEVELS OF 17-
HYDROXYPROGESTERONE, AND USG -- RAPID
DIAGNOSIS.
• DD:
– TRUE HERMAPHORDITISM
– PSEUDOHERMAPHRODITISM
– SEX CHROMOSOME ABNORMALITIES
• NONE HAVE HIGH 17-
HYDROXYPROGESTERONE.

16. • DIAGNOSIS
DIAGNOSIS IS BASED ON ELEVATED 17-OHP LEVELS IN PRESENCE OF
CLINICAL PICTURE.
• ◦ SHOULD BE PERFORMED ONLY IN THE MORNING
• ◦ IN NEONATAL PERIOD, THE LEVELS MUST BE MEASURED AFTER
48 HRS OF LIFE DUE TO EFFECT OF NEONATAL SURGE.
• ACTH STIMULATION TEST :
• ◦ MEASUREMENT OF 17 OHP LEVELS, 1 HR AFTER
ADMINISTRATION OF 250 MCG OF IV COSYNTROPIN A SYNTHETIC
ACTH
• ◦ DONE IN INDIVIDUALS WITH BORDERLINE 17 OHP LEVELS.
• >10,000 NG/DL CLASSIC (BOTH SW&SV)
• 1000 – 10,000 NG/DL NON-CLASSIC
• <1000 NG/DL NORMAL
• ◦ ELEVATED PLASMA RENIN ACTIVITY (PRA) VALUES,
PARTICULARLY THE RATIO OF PRA TO ALDOSTERONE, ARE
MARKERS OF IMPAIRED MINERALOCORTICOID SYNTHESIS

17. • TREATMENT
• ALL FORMS- GLUCOCORTICOID
(HYDROCORTISONE)REPLACMENT THERAPY.
– ALLEVIATES GLUCOCORTICOID DEFICIENCY
– PROVIDES NEGATIVE FEEDBACK TO
SUPPRESS ACTH SECRETION AND PREVENT
CONTINUED ADRENAL STIMULATION.
– AS A RESULT, EXCESSIVE 17-
HYDROXYPROGESTERONE IS N/A AS A
SUBSTRATE FOR EXCESSIVE ANDROGEN
PRODUCTION.
• PATIENTS WITH THE SALT-WASTING FORM –
ALSO NEED

18. • PRENATAL TREATMENT OF MOTHER
WITH GLUCOCORTICOIDS CAN
PREVENT/REDUCE THE VIRILIZING
EFFECTS OF FETAL 21-HYDROXYLASE
DEFICIENCY (PREVIOUS AFFLICTED
BABIES; AR INHERITANCE).
• AFTER COMPLETION OF GROWTH
,SYNTHETIC GLUCOCORTICOID
PREPARATION(DEXAMETHASONE,PREDN
ISOLONE)CAN BE USED
• SURGICAL CORRECTION OF GENITAL
ANOMALIES AND GENDER REASSIGNMENT
IN ADULTS.

19. OTHER FORMS OF
CAH
Deficiency Incidence Comments
11 beta-
hydroxylase
1 in 100,000
livebirths
Females virilized; salt-wasting is rare
17 alpha-
hydroxylase
rare
Males virilized; females fail to
achieve puberty. Salt-wasting not
observed.
3 beta-
hydroxysteroid
dehydrogenase
rare
Males virilized; female virilization
mild. Salt-wasting may be seen.
aldosterone
synthase
rare
Cortisol normal and virilization not
seen. Salt-wasting occurs.
StAR rare
Males virilized; females fail to
achieve puberty. Salt-wasting occurs.