Molecular Characterization of a Leydig Cell Tumor Presenting as Congenital Adrenal Hyperplasia*

Abstract

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.

Ten-Year Follow-Up in a Boy with Leydig Cell Tumor after Selective Surgery

“…It can be both unilateral [16]or bilateral [17]. Leydig cell tumors may produce minimally or even greatly elevated plasma 17-OHP levels [18, 19]. Our patient showed a moderately 4- to 5-fold) elevated plasma 17-OHP concentration.…”

Virilizing adrenal tumour mimicking congenital adrenal hyperplasia with P450c11 (11β-hydroxylase) deficiency

“…A testicular Leydig cell tumour RNA was available from a previously described 3.5-year-old boy who presented with accelerated growth rate, phallic enlargement, and pubic hair. His clinical picture and steroid findings mimicked congenital adrenal hyperplasia due to 21-hydroxylase deficiency [19].…”

“…1 Northern blot analysis of P450scc and c21 mRNAs in fetal adrenal, normal adult adrenal (from a patient operated for a kidney tumour), the present case of virilizing adrenal adenoma and in a testicular Leydig cell tumour [19]. Each lane had 30 gg total RNA.…”

“…One RNA filter was sequentially hybridized with the three probes. The migration of 28S and 18S ribosomal RNAs are indicated Table 2 Relative expression of different steroidogenic enzyme mRNAs in normal adult adrenal, the virilizing adrenal adenoma, fetal adrenal, and in a testicular Leydig cell tumour [19]. The data are based on scanning readings of the autoradiographs of a dot blot filter (two gg total RNA in each dot) which was sequentially hy~bridized with each probe.…”

“…The only significant abnormality in the expression of the steroidogenic enzymes in the virilizing adenoma was its low P 4 5 0 c l l m R N A content (Fig.2). Table 2 shows the relative expression of the different steroidogenic mRNAs (based on the scanning readings of the autoradiographs of a dot blot filter) in the virilizing adenoma, normal adult adrenal, normal fetal adrenal and in a testicular Leydig cell tumour [19].…”