Plasma Pregnenolone and 17-OH-Pregnenolone in Patients with Adrenal Tumors, ACTH Excess, or Idiopathic Hirsutism1

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Abstract
Plasma levels of the Δ5-pregnenes, pregnenolone and 17-OH-pregnenolone, were measured in patients with disordered steroidogenesis. While 17-OH-pregnenolone was within the normal range in patients with hypercortisolemia due to Cushing's disease, ectopic ACTH or adrenal adenoma, 4 of 6 patients with an adrenal carcinoma had elevated levels of this precursor. Thus, elevated plasma 17-OH-pregnenolone levels in patients with Cushing's syndrome indicate adrenal carcinoma, although a normal value does not exclude this diagnosis. Abnormal resistance of Δ5-pregnenes to suppression with dexamethasone proved useful in detecting the presence of residual tumor in the post-operative evaluation of adrenal carcinoma. Basal plasma pregnenolone was within the normal range in 19 of 20 patients with Cushing's disease and was invariably normal in patients with other varieties of hypercortisolism. Since acute administration of ACTH causes marked elevation of Δ5-pregnene levels while patients with chronic ACTH excess (Cushing's disease and ectopic ACTH production) have normal levels, it is suggested that ACTH has a chronic influence on the intraadrenal utilization of Δ5-pregnenes in addition to stimulating their formation. In pre-menopausal women with idiopathic hirsutism, basal levels of both Δ5-pregnenes were elevated (P <0.001). Following dexamethasone administration the absolute decrease in Δ5-pregnene levels was greater than that seen in normal subjects. This observation indicates that the metabolism of Δ5-pregnenes is abnormal in patients with idiopathic hirsutism.

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