62. Adrenal hyperandrogenism (adrenogenital syndrome) - etiology, pathogenesis, clinical manifestations.

Adrenal hyperandrogenism (adrenogenital syndrome) – etiology, pathogenesis, and clinical manifestations.

Adrenal hyperandrogenism refers to excess production of adrenal androgens, leading to virilization or masculinization, especially in females.

When caused by enzyme defects (congenital), it is known as congenital adrenal hyperplasia (CAH).

Etiology

Congenital causes (most common)

Congenital adrenal hyperplasia (CAH) due to enzyme deficiencies in cortisol synthesis pathway.

Most common defect: 21-hydroxylase deficiency (~90% of cases).

Other rare enzyme deficiencies:

• 11β-hydroxylase deficiency.
• 17α-hydroxylase deficiency.
• 3β-hydroxysteroid dehydrogenase deficiency.

Acquired causes

Androgen-producing adrenal tumors (adenomas or carcinomas).

ACTH-producing tumors stimulating adrenal cortex (rare).

Pathogenesis

In congenital adrenal hyperplasia (CAH)

1. Enzyme deficiency → reduced cortisol synthesis.
2. Low cortisol → loss of negative feedback on hypothalamus and pituitary → increased ACTH secretion.
3. Chronic ACTH stimulation → adrenal cortical hyperplasia.
4. Steroid precursors diverted into androgen synthesis pathway → excess androgens.
5. Possible aldosterone deficiency (salt-wasting form, especially in 21-hydroxylase deficiency).

In acquired forms

Tumor directly secretes excess androgens → similar effects.

Clinical manifestations

In females

Virilization:

• Clitoromegaly.
• Labial fusion.
• Hirsutism (excess facial/body hair).
• Deep voice.
• Male-pattern baldness.
• Acne.

Menstrual irregularities or primary amenorrhea.

In males

Prepubertal boys:

• Precocious pseudopuberty (early development of secondary sexual characteristics without testicular enlargement).
• Accelerated linear growth initially, but premature epiphyseal closure → short final adult stature.

Adult men:

• Often subtle; sometimes infertility due to testicular adrenal rest tumors.

Salt-wasting form (in CAH)

Features of aldosterone deficiency:

• Hyponatremia.
• Hyperkalemia.
• Hypotension.
• Dehydration.

Other features

Hyperpigmentation (due to high ACTH stimulating melanocytes).

Rapid somatic growth but early growth plate fusion → short stature.

Summary Table