CAH - CONGENITAL ADRENAL HYPERPLASIA

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ongenital Adrenal Hyperplasia or CAH, is a disorder which is characterised by defects in enzyme that lead to various effects. 

The most common enzyme affected in CAH is 21 hydroxylases enzyme. The second most common enzyme to be affected is 11-β-hydroxylase enzyme. The gene CYP 21A₂ is affected, this is the same gene that codes for 21 hydroxylases.

The following image shows the steroid pathway that takes place in the adrenal glands, where cholesterol is the basic material used for synthesis. 

Here 21 OH stands for 21 Hydroxylase, 11 beta signifies 11-β-hydroxylase.

As the normal physiological process, 21 hydroxylase enzyme acts as an important enzyme for synthesis of corticosteroids and mineralocorticoids.

As there is 21 hydroxylase deficiency there will be reduction in the production of corticosteroids and mineralocorticoids.

Due to deficiency of mineralocorticoids, there will be salt and water wasting.

As the levels of corticosteroids decrease, there is a negative feedback on ACTH (adreno-cortico-tropic-hormone). This causes an increase in ACTH that triggers adrenal glands to produce more and more of corticosteroids and mineralocorticoids. This further worsens the case as increased production of corticosteroids mean increase in progesterone production, increase in 17 hydroxy progesterone and Androgens. Due to increase in androgens the following effects are seen –

1.    External genitalia resembles that of male – Ambiguous genitalia

2.    Short stature

3.    Virilization

4.    Precocious puberty

Precocious puberty in females lead to –

1.    Clitoromegaly

2.    Deepening of voice

3.    Hirsutism

4.    Increase in muscle mass

5.    Virilization

 

This image shows early development of breasts in a young female child indicating precocious puberty.

Another enzyme involved in CAH is 11-β-hydroxylase. In this case, corticosteroid and mineralocorticoids are not formed instead, androgens and progesterone are formed and deoxy-cortisone levels are more this causes hypertension.

The following things are increased in 11-β-hydroxylase deficiency –

1.    Progesterone

2.    17 hydroxy progesterone (mildly)

3.    Androgens

4.     Deoxy-cortisone

This leads to –

1.    Hypertension

2.    Ambiguous genitalia in female

Female with ambiguous genitalia

Screening test for CAH –

17 hydroxy-progesterone levels are checked. In this test we inject ACTH and then wait for 30 mins, after which the blood sample is checked for 17 hydroxy-progesterone levels. If the levels are above 1500 nanogram, it is definitive case of CAH. This diagnostic test is done only when the serum levels are in the range of 300 – 800 nanogram (before injecting ACTH for the screening).

Management –

To correct the mineralocorticoid defect, we add Fludrocortisone

To correct the corticosteroid defect, we add corticosterone.

Surgical option is present where we do corrective surgery, i.e. removal of phallus at the age of 4 or age of 5.

According to age, if the child has not hit puberty, we administer hydrocortisone.

If he/she is at puberty we administer prednisolone or dexamethasone.

If the CAH is not at the birth, then sometimes it may occur at or after the puberty. This is called as late onset CAH and is characterised by –

1.    Reduced cortisol

2.    Reduced mineralocorticoids

3.    Increased progesterone

4.    Increased androgen at puberty

Thus, the clinical features are –

1.    Female external genitalia

2.    Virilization

3.    Hirsutism

4.    Deep voice

5.    Increased muscular mass

Virilization means a female that resembles male secondary sexual characteristics.

Differential diagnosis – PCOS (Poly-Cystic-Ovarian-Syndrome)

 

Hirsutism