We present an unusual patient with a Leydig cell tumor to show that greatly elevated serum concentrations of 17-hydroxyprogesterone (17OHP) may not be diagnostic of congenital adrenal hyperplasia (CAH). A 3.5-yr-old boy had a small testicular mass and plasma 17OHP concentrations of 147-333 nmol/L (4,850-11,000 ng/dL), suggesting CAH with adrenal rests. However, normal plasma cortisol values and the unresponsiveness of the 17OHP concentration to dexamethasone suppression or ACTH stimulation suggested a diagnosis of Leydig cell tumor. A 4-fold elevation in plasma 21-deoxycortisol compared with a 200-fold elevation in 17OHP suggested that the elevated 17OHP derived from the normal pathway of testosterone synthesis in the testis. This was proven by normalization of all hormonal values after tumor resection. Compared to the abundance of mRNA for P450c17, the tumor contained unusually large amounts of mRNA for P450scc, the cholesterol side-chain cleavage enzyme, which is the rate-limiting step in steroid hormone synthesis. Increased P450scc activity, which increased the conversion of cholesterol to pregnenolone, apparently permitted the 17,20-lyase activity of P450c17 to become rate limiting, thus accounting for the increased secretion of 17OHP. Thus, Leydig cell tumors can produce quantities of 17OHP previously reported only in CAH due to 21-hydroxylase deficiency. The molecular characterization of steroidogenic mRNAs in this tumor indicates an unusual ratio in the expression of the genes for the steroidogenic enzymes, probably accounting for the unusual pattern of serum steroids.
