Question 1

What is the Meaning of Congenital Lipoid Adrenal Hyperplasia?

Accepted Answer

Congenital Lipoid Adrenal Hyperplasia (CLAH) is a rare autosomal recessive genetic disorder causing a severe inability to synthesize adrenal and gonadal steroid hormones. This condition stems from a critical defect in the initial step of steroidogenesis: cholesterol transport into mitochondria. Individuals experience a severe, global deficiency of all steroid hormones, including glucocorticoids, mineralocorticoids, and sex steroids, from birth.

Question 2

What is the Context of Congenital Lipoid Adrenal Hyperplasia?

Accepted Answer

This disorder directly affects the adrenal cortex, the primary site of steroid hormone production. CLAH disrupts the essential function of the steroidogenic acute regulatory protein (StAR), a key component in the endocrine pathway for cholesterol transport. Despite normal pituitary ACTH stimulation, adrenal glands cannot process accumulated cholesterol into necessary steroid precursors, leading to their characteristic lipid-laden appearance.

Question 3

What is the Significance of Congenital Lipoid Adrenal Hyperplasia?

Accepted Answer

Clinically, CLAH presents as a life-threatening neonatal emergency due to severe adrenal insufficiency. Affected infants experience salt-wasting crises, manifesting as severe dehydration, hypotension, and electrolyte imbalances, necessitating immediate medical intervention. Genetic males often exhibit ambiguous external genitalia at birth due to absent fetal androgen production, requiring careful diagnostic evaluation and specialized management.

Question 4

What is the Mechanism of Congenital Lipoid Adrenal Hyperplasia?

Accepted Answer

The underlying molecular defect in Congenital Lipoid Adrenal Hyperplasia is typically a mutation in the STAR gene, encoding the steroidogenic acute regulatory protein. This protein is crucial for moving cholesterol from the outer to the inner mitochondrial membrane, the rate-limiting step in steroid hormone synthesis. Dysfunctional StAR causes cholesterol accumulation, preventing conversion to pregnenolone and halting the steroid synthetic cascade.

Question 5

What is the Application of Congenital Lipoid Adrenal Hyperplasia?

Accepted Answer

Management of CLAH involves immediate and lifelong hormone replacement therapy. Infants receive glucocorticoids and mineralocorticoids to prevent adrenal crises and maintain electrolyte balance. Sex steroid replacement becomes necessary at puberty for secondary sexual characteristic development. Regular clinical monitoring and dose adjustments are essential for optimizing patient health.

Question 6

What is the Metric of Congenital Lipoid Adrenal Hyperplasia?

Accepted Answer

Diagnosis of Congenital Lipoid Adrenal Hyperplasia relies on biochemical and genetic confirmation. Laboratory tests reveal extremely low or undetectable levels of cortisol and aldosterone, coupled with markedly elevated plasma ACTH. Electrolyte panels often show hyponatremia and hyperkalemia. Definitive diagnosis is established through genetic sequencing to identify pathogenic mutations in the STAR gene.

Question 7

What is the Risk of Congenital Lipoid Adrenal Hyperplasia?

Accepted Answer

Without timely diagnosis and appropriate hormonal intervention, individuals with CLAH face severe, potentially fatal risks from acute adrenal crises. These crises can lead to circulatory collapse, severe electrolyte disturbances, and metabolic acidosis, demanding immediate critical care. Long-term risks from inadequate hormone replacement include chronic fatigue, poor growth, and recurrent infections. Consistent medical supervision and strict adherence to prescribed hormone regimens are paramount.

Congenital Lipoid Adrenal Hyperplasia

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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