Pregnenolone, Mass Spectrometry (Endocrine Sciences)

In humans, steroid hormones are produced by the adrenal glands and the gonads.^1,2 The formation of pregnenolone from cholesterol is the first step in steroidogenesis and is mediated by the proteolytic enzyme, single cholesterol side-chain cleavage enzyme (P450 scc). Steroidogenesis continues along two paths from pregnenolone. 17-Hydroxypregnenolone is produced from pregnenolone through the enzymatic action of 17α-hydroxylase (17α-H). Alternatively, pregnenolone is converted to progesterone through the enzymatic action of 3β-hydroxysteroid dehydrogenase (3β-HSD).

Pregnenolone levels have been shown to remain in the normal range in patients with Cushing syndrome and hyperaldosteronism.^3,4 Levels can be suppressed with dexamethasone inhibition and increased with exogenous ACTH stimulation.³ Pregnenolone levels have been shown to be elevated in patients with idiopathic hirsutism.⁴

Since the various forms of congenital adrenal hyperplasia (CAH) result from enzymatic defects in the adrenal steroidogenic pathways, measurement of pregnenolone levels can be useful in diagnosis. Pregnenolone levels tend to be elevated in several forms of CAH, particularly in 17α-H deficiency and 3β-HSD deficiency since these enzymes catalyze steps immediately after pregnenolone in the steroidogenic pathways.²