CONGENITAL ADRENAL HYPERPLASIA

CONGENITAL ADRENAL HYPERPLASIA (CAH)

CAH is a familial autosomal recessive disorder of adrenal steroid biosynthesis in which one of enzyme necessary for cortisol production has defiant activity.

Decreased serum cortisol levels stimulate adrenocorticotropic hormone (ACTH) release via negative feedback. The adrenal glands undergo hypertrophy, apparently due to ACTH-stimulated production of insulinlike growth factor 2. Increased ACTH secretion also results in overproduction of both the adrenal steroids preceding the missing enzyme and those that do not require the missing enzyme.

Aldosterone (mineralocorticoid) synthesis and secretion is regulated via renin-angiotensin system (adrenal zone glomerulosa), which is responsive to the electrolyte balance state and plasma volume. Aldosterone secretion is also directly stimulated by high serum potassium concentrations.

Cortisol (glucocorticoid) synthesis and secretion is regulated by ACTH (adrenal zone fasciculate), which stimulates the enzyme P-450scc (20, 22 Desmolase) with subsequent increased production of all adrenal steroids.

Approximately 80-90 % of individuals with ACH have 21α-hydroxylase deficiency: ↓ cortisol (increased ACTH), ↓ mineralocorticoids, ↑ sex hormone. Masculinization, female pseudohermaphroditism, hypotension, hyperkalemia, ↑ plasma rennin activity, and volume depletion. Salt wasting can be lead to hypovolemic shock in the newborn.

The second most common types of ACH is the 11β-hydroxylase deficiency, it has an incidence of about 1 in 100.000.

Finding: ↓ cortisol, ↓ Aldosterone and Corticosterone, ↑ sex hormones

Masculinization, hypertension (like Aldosterone, 11-deoxycorticosterone is a mineralocorticosteroids and is secreted in excess).

17α-hydroxylase deficiency is probably even more rare genetic disorder of steroid biosynthesis that causes decreased production of glucocorticoids and sexual steroids, and increased synthesis of mineralocorticoids precursors.

Finding: ↓ sex hormone, ↓ cortisol, ↑ mineralocorticoids.

Hypertension, hipokalemia.

XY: ↓ Dihydrotestosterone → pseudohermaphroditism (external phenotypic female, no internal reproductive structure).

XX: external phenotypic female with normal internal sex organs, but lacking secondary sexual characteristics (sexual infantilism).

Hypogonadism occurs as a result of deficient sex steroid production. Deoxycorticosterone mineralocorticoid activity causes sodium retention, plasma volume expansion, hypertension, hipokalemia, and decreased renin and Aldosterone levels in most untreated patients with 17α-hydroxylase deficiency.

Exogenous glucocorticoid therapy is the treatment of choice.

All congenital adrenal enzyme deficiencies are characterized by an enlargement of adrenal glands due to an ↑ in ACTH stimulation because of the ↓ levels of cortisol.