Activation of Testicular Adrenal Rest Tissue by Prolonged Excessive ACTH Production

Abstract

The concept that continuous excessive ACTH production can cause tumorous hyperplasia of “adrenal rest” cells within the testis is supported by studies in the patient reported here, who appears to represent the first reported instance of a cortisol⁴-producing testicular tumor in recurrent Cushing's disease. A 14-year-old boy who had had a subtotal adrenalectomy and subtotal resection of a pituitary tumor presented with signs of recurrent glucocorticoid excess associated with the development of a testicular tumor. Urinary 17-ketosteroids, 17-hydroxysteroids and plasma ACTH levels were elevated. ACTH stimulation and dexamethasone suppression suggested an autonomous steroidproducing tumor. Removal of the testicular tumor produced symptomatic improvement, with a reversion to normal of the urinary steroids in spite of persistence of pigmentation. Histologically, the tumor was reported to be either an interstitial tumor of testicular origin or an adrenal rest tumor. Incubation studies of the tumor with C¹⁴-labeled precursors resulted in the production of cortisol and the demonstration of 6β-,11β-,17α-, and 21-hydroxylase activity. This evidence supports the hypothesis that the tumor was of adrenal rest origin.