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Pregnenolone, Serum

Measurement of serum pregnenolone is used as an ancillary test mainly for the diagnosis of congenital adrenal hyperplasia (CAH).

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Pregnenolone is the first steroid to be derived from cholesterol in the pathway of steroidogenesis, and it is the common precursor for all adrenal and gonadal steroids. Its production occurs in the mitochondria by cleavage of the C-20 side chain of cholesterol by the P-450SCC enzyme. Once produced, pregnenolone may be utilized by two pathways of steroidogenesis. Pregnenolone may either be converted to 17-OH pregnenolone via the enzymatic action of 17α-hydroxylase or to progesterone via the enzymatic action of 3β-hydroxysteroid dehydrogenase.

Elevated pregnenolone levels occur in different forms of congenital adrenal hyperplasia, due to 3β-hydroxysteroid dehydrogenase deficiency or 17α-hydroxylase deficiencies. Higher levels have also been reported in women with idiopathic hirsutism.

Pregnenolone levels have been shown to remain in the normal range in patients with Cushing syndrome and hyperaldosteronism.

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