Cortisol Production by Testicular Tumors in a Patient with Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)*

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Abstract
Bilateral testicular tumors are known to occur in congenital adrenal hyperplasia, but their steroidogenic properties are not well studied. We have recently demonstrated steroid 11β-hydroxylase activity in these tumors from a 27-yr-old patient with documented salt-losing congenital hyperplasia (21-hydroxylase deficiency). Spermatic venous blood obtained at operation contained 3.6—5 ng/ml cortisol, as measured by specific RIA after Sephadex LH-20 chromatography. In contrast, the peripheral venous cortisol level was 0.64 ng/ml. The presence of 11β- hydroxylase activity was demonstrated by the in vitro conversion of [3H]deoxycorticosterone to [3H]corticosterone in tumor tissue. The conversion ratio of deoxycorticosterone to corticosterone was 4.3% and 7.07%/mg tissue in the tumor tissue, whereas in normal testicular tissue, it was less than 1%. The radiochemical identity of corticosterone was confirmed by rechromatography on Sephadex LH-20, coelution with added [14C]corticosterone, and a constant 3H to I4C ratio after acetylation and thin layer chromatography. The tumor cells grown in primary culture, produced steroids and responded to ACTH and hCG. Electron microscopy of the tumor revealed a large number of mitochondria containing electron dense granules. Light microscopy was compatible with Leydig cell tumor. In conclusion, testicular tumors in association with congenital adrenal hyperplasia have morphological features of Leydig cells but have the capability of llβ-hydroxylation and cortisol production, properties which are unique to adrenocortical tissue. These findings suggest that they originate from pluripoter.tial cells in the testicles. Regression of these tumors has been reported with optimal biochemical control of the disease.