Evidence for Endogenous LH Suppression in a Man with Bilateral Testicular Tumors and Congenital Adrenal Hyperplasia1

Abstract

The need for a functional classification of “Leydig cell” tumors in men with congenital adrenal hyperplasia (CAH) is exemplified by the present case of a 19 year old boy with this disorder, who developed bilateral testicular masses despite replacement with hydrocortisone. During basal conditions, in which he received hydrocortisone, 25 mg/day, urinary 17-ketosteroids and pregnanetriol were 33 and 18.5 mg/24 h, respectively. Concomitantly, mean plasma 17-hydroxy-progesterone (17OHP) concentrations, 32.2 (A.M.), 58.8 (P.M.), ng/ml, were increased 30–50-fold, while mean plasma cortisol (F), 7.7 (A.M.), 12.3 (P.M.) μg/dl, testosterone (T), 485 (A.M.) 493 (P.M.) ng/dl and estradiol (E2) 12.4 (A.M.), 16.3 (P.M.) pg/ml, concentrations were within normal limits. Episodic fluctuations of plasma T, E2 and 170HP were demonstrated in both morning and afternoon samples, with pulses occurring at approximately 90 min intervals. By contrast plasma LH levels, pulsatile in the morning, fell in the afternoon with no evident episodic release. Mean morning plasma LH, 13.9 ± 4.8 (SD) was significantly higher than that of afternoon (8.0 ± 3.8) MIU/ml, P < 0.01. Following 48 h of ACTH suppression with dexamethasone mean plasma 17OHP and F concentrations fell to 1–2 ng/ml and 2–3 μg/dl, respectively. Concomitantly, mean afternoon plasma T, E2 concentrations decreased (29%) with pusatile fluctuations preserved, and mean afternoon plasma LH concentration increased 4-fold and episodic release was reestablished. Peaks of plasma LH preceded those of T, E2 and 17OHP by 30 min. Six days of ACTH suppression with dexamethasone resulted in a fall of urinary 17KS and pregnanetriol to 12.3 and 4.3 mg/24 h, respectively. The enlarged testes decreased to normal size after ACTH suppression with dexamethasone. During adrenal stimulation with ACTH the tests re-enlarged and spermatic venous F (14.3 μ/dl) and 17OHP (557 ng/ml), were 3-fold higher than simultaneous peripheral levels of F (5.2 μ/dl) and 17 OHP (196 ng/ml). Light and electron microscopic findings of the tumor were consistent with “Leydig cells” although no Reinke's crystals were observed. In the normal testicular tissue, seminiferous tubules revealed maturation arrest of germ cells at spermatocyte level. These data suggest that 1) the functional capacity of “Leydig cell” tumors in CAH may not correlate with morphological appearance, 2) such tumors may secrete cortisol and demonstrate ACTH dependence and 3) endogenous suppression of LH secretion may occur during periods of inadequate ACTH suppression.