Congenital Adrenal Hyperplasia

Vijayakumar Madhava
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Glucocorticoid Supplementation
Daily requirement of cortisol for effective suppression of ACTH and adrenal androgen production is about 10-15 mg/m2. Neonates and newly diagnosed patients require higher dose (15-20 mg/m2) initially to suppress their hyperactive CRH-ACTH- adrenal axis. Various glucocorticoid dose equivalents are based on their anti inflammatory properties, and growth suppressing effect does not match with anti inflammatory properties. Dexamethazone and prednisolone have powerful growth suppressant effects compared to hydrocortisone. Hence these drugs are better avoided in children. But it can be used in adults where epiphyseal fusion has already completed.

Its use is well established in salt loosing variety of CAH. In simple virilizing types also it is advised because in these children the dose of glucocorticoids can be reduced and hence the growth suppression and weight gain can be avoided. The only mineralocorticoid available at present is fludrocortisone. Neonates require larger doses of fludrocortisone (0.15-0.3 mg/day) compared to older children (0.05- 0.15 mg/day).
For the action of mineralocorticoids, there should be an adequate amount of sodium in the renal tubule. Hence additional salt supplementation (1-2 g of NaCl/day) is required in early infancy.

Table 5 : Maintenance therapy in children with CAH
Drug Total daily dose Daily distribution
Hydrocortisone 10- 15 mg/m2 3 times
Fludrocortisone 0.05 – 0.2 mg 1-2 times
Sodium chloride supplementation 1-2 grams (17-34 mEq/day) in infancy Divided in several feedings


Effective management requires close monitoring. Growth measurements should be made at 4-6 monthly intervals. Bone age should be assessed every year. Blood pressure is recorded in each visit. Measurement of serum electrolytes ( Na, k) should be performed in each visit. PRA and 17 OHP measurements are done at least once a year. Attempts to completely normalize 17- OHP levels result in over treatment. Children with good treatment protocols have mildly elevated 17-OHP levels. Dose adjustment is made based on overall clinical profile and anthropometric measurements rather than based on 17-OHP value alone.

Children with CAH are unable to produce enough cortisol in response to stressful situations like febrile episodes, diarrhea, surgery or trauma. They require increased dose of glucocorticoids (hydrocortisone) in such situations. When pharmacological dose of hydrocortisone is given, mineralocorticoids are not required because pharmacolological dose of hydrocortisone has enough mineralocorticoid action. Patient should be given glucose and electrolyte supplementation and should never be allowed to fast. The initial stress dose of hydrocortisone is 60- 100 mg/m2. Subsequent doses are given as 3-4 times maintenance dose of hydrocortisone per day, divided every 6 hours.

Table 6: Initial stress dose of hydrocortisone in different age groups
Age groups Weight groups (kg) Dose of hydrocortisone (mg)
< 6 months < 7 25
6 months – 2 years 8-12 50
3 – 10 years 13-30 75-100
> 10 years >30 100-200


Surgical reconstruction should be considered in infancy itself in a severely virilized child (Prader stage >3). In less virilized children clitoroplasty and vaginoplasty can be done at a later age.

Prenatal treatment continues to remain as experimental. This method is based on the fact that suppression of fetal adrenal androgen in CAH can be achieved by administering glucocorticoids to the mother. This will reduce the genital virilization of the affected girl child and reduce the need for genital reconstructive surgery. The drug used is dexamethasone since this drug is not inactivated by placental 11ß- HSD2. The treatment must be started at 6-7 weeks of gestation. Fetal DNA is obtained by chorionic villous sampling at 10-12 weeks. The therapy is continued only if the fetus is a girl.

This treatment results in various maternal problems. These include weight gain, pedal edema, hypertension, striae, gestational diabetes and mood swings. In fetus it may develop cleft palate and other craniofacial abnormalities.

Table 7: presentation of different types of CAH
Type Presentation Laboratory findings  
Lipoid CAH Salt wasting crisis

Under virilized male
Low levels of all steroid hormones

Decreased response to ACTH

High ACTH & PRA
Gluco and mineralo corticoid replacement

Salt supplementation

Estrogen replacement at puberty

Gonadectomy for male
3ß HSD Salt wasting crisis

Under virilized male
High d 5 steroids

High ACTH & PRA
Gluco and mineralo corticoid replacement

Salt supplementation

Genital surgical correction
21- Hydroxylase deficiency Salt wasting crisis

Virilized female
High 17-OHP

High serum androgens

High ACTH & PRA
Gluco and mineralo corticoid replacement

Salt supplementation

Surgical genital correction in girls
11 ß hydroxylase deficiency Virilized female

Hypertension
High 11- Deoxy cortisol and Deoxy corticosterone

High 17- OHP

High ACTH, Low PRA

Hypokalemia
Glucocorticoid replacement

Surgical genital correction in girls
17 a hydroxylase deficiency Under virilized male

Hypertension
High DOC, corticosterone,

High ACTH, low PRA

Hypokalemia
Glucocorticoid administration

Surgical correction of genitalia and sex steroid replacement in boys


Treatment of CAH is a double edged sword. Over treatment results in linear growth failure, hypertension and cushingoid features. Under treatment results in lack of effective suppression of adrenal androgen production resulting in early epiphyseal fusion and short stature.


References
Congenital Adrenal Hyperplasia Congenital Adrenal Hyperplasia 03/18/2016
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