Feminizing Testicular Leydig Cell Tumor: Hormonal Profile before and after Unilateral Orchidectomy*

Abstract Background: Sertoli-Leydig cell tumors account for less than 1% of ovarian tumors, and information about their biochemical markers has been lacking. Objective: The objective was to characterize the hormonal profile of Sertoli-Leydig cell tumor, which should be helpful in recognizing this rare condition in the future. Methods: We reviewed test results including serum total and free testosterone, steroid hormone precursors, and inhibin B levels in a 17-year-old adolescent girl with ovarian Sertoli-Leydig cell tumor who developed secondary amenorrhea for 6 months, deepening of the voice, acne, and severe hirsutism. Results: Our patient had serum testosterone 641 ng/dL (expected 20 - 38), dihydrotestosterone 42.5 ng/dL (expected 3 - 18), 17-OH progesterone 659 ng/dL (expected 20 - 265), androstenedione 869 ng/dL (expected 50 - 224), 17-OH pregnenolone 760 ng/dL (expected 53 - 357), DHEA 1250 ng/dL (expected 4 - 491), and DHEA-S of 366 mcg/dL (expected 44 - 248). Inhibin B level was 321 pg/mL (expected <136); inhibin A was normal. Anti-mullerian hormone, a-fetoprotein, carcinoembryonic antigen, and CA-125 tumor markers were not elevated. Karyotype was female 46,XX. Dexamethasone 0.5 mg QID PO for 4 days resulted in plasma ACTH <5.0 pg/mL and serum cortisol <1.0 mcg/dL, total testosterone 611 ng/dL, free testosterone 25.1 ng/dL (expected <0.04 - 1.09 ng/dL), and 17-OH progesterone 887 ng/dL. Abdomen and pelvis MRI demonstrated a right ovarian mass primarily solid with high cellularity, measured 4.4 x 3.9 cm; there was at least moderate diffuse enhancement of the mass after contrast administration; adrenal glands were normal. Surgical pathology of the resected right ovary revealed moderately to poorly differentiated Sertoli-Leydig cell tumor. Single antibody immunostain procedures with appropriate controls showed a staining pattern supportive of this rare diagnosis: WT-1 showed moderate nuclear staining, calretinin showed a strong positive stain, and CK showed a patchy moderate staining pattern; immunostains for myogenin, desmin, and EMA were negative. Genetic testing revealed a germline heterozygous mutation in DICER1 gene, c3737del, p.Asn1246Metfs*12, establishing the diagnosis of DICER1 syndrome, an autosomal dominant disorder predisposing to cancer. Menses resumed one month after tumor resection. Conclusions: High serum 17-OH progesterone, androstenedione, 17-OH pregnenolone, and DHEA levels used as indicators of adrenocortical function could be markers of an ovarian tumor. If serum 17-OH progesterone and testosterone remain high when cortisol and plasma ACTH are suppressed on Dexamethasone test, a source of 17-OH progesterone and testosterone is other than ACTH-dependent adrenal one. High serum inhibin B level may be sign of an ovarian tumor. Patients with Sertoli-Leydig cell tumor should be screened for DICER1 gene syndrome to assess risk for other rare neoplasms.

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Characterization of a feminizing testicular leydig cell tumor by hormonal profile, immunocytochemistry, and tissue culture

Cancer ◽

10.1002/1097-0142(19851001)56:7<1667::aid-cncr2820560733>3.0.co;2-1 ◽

1985 ◽

Vol 56 (7) ◽

pp. 1667-1676 ◽

Cited By ~ 11

Author(s):

Helen Czernobilsky ◽

Bernard Czernobilsky ◽

Hans G. Schneider ◽

Werner W. Franke ◽

Reinhard Ziegler

Keyword(s):

Tissue Culture ◽

Leydig Cell ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Hormonal Profile

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Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis

Acta Endocrinologica ◽

10.1530/eje.0.1310156 ◽

1994 ◽

Vol 131 (2) ◽

pp. 156-159 ◽

Cited By ~ 10

Author(s):

Philippe J Caron ◽

Antoine P Bennet ◽

Monique M Plantavid ◽

Jean-Pierre Louvet

Keyword(s):

Luteinizing Hormone ◽

Leydig Cell ◽

Half Life ◽

Pulse Amplitude ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Pulse Interval ◽

Before And After ◽

Lh Secretion ◽

Secretory Pattern

Caron PJ, Bennet AP, Plantavid MM, Louvet J-P. Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis. Eur J Endocrinol 1994;131:156–9. ISSN 0804–4643 We studied the luteinizing hormone (LH) secretory pattern in three patients, aged 30, 23 and 43 years, with gynecomastia due to Leydig cell tumor of the testis, before and 6 months after unilateral orchidectomy. The results were compared to those of 11 normal fertile controls aged 20–35 years. Blood sampling was done at 20-min intervals from 22.00 h to 10.00 h. The LH data were analyzed with the Cluster analysis algorithm with "optimal parameters for LH male data" to determine the pulse interval and pulse amplitude. The Expfit program was applied to LH pulses to calculate the apparent half-life of immunoreactive LH. Before surgery, when compared to controls, the patients had a low to normal testosterone/estradiol ratio (0.053, 0.110, 0.046 vs 0.148 ± 0.038) and mean LH levels (1.96, 3.7, 2.55 vs 4.0 ± 1.9 IU/l), decreased pulse amplitude (2.65, 3.01, 2.21 vs 3.31 ± 1.41 IU/l) and reduced apparent half-life of LH (74, 69, 78 vs 97 ± 16 min). After removal of the Leydig cell tumor, the testosterone/estradiol ratio returned to the normal range (0.141, 0.177, 0.093) while an increase in mean LH levels (5.75, 7.90, 4.88 IU/l), LH pulse amplitude (3.07, 6.05, 2.86 IU/l) and apparent half-life of LH (138, 106, 104 min) was observed in all three patients. Our data indicate that endogenous hyperestrogenism in patients with Leydig cell tumor of the testis results in an inhibition of LH secretion, and suggests that such inhibition could result from a reduction in pulse amplitude and apparent half-life. Philippe Caron, Service d'Endocrinologie et Maladies métaboliques, CHU Rangueil, 1 Avenue J Poulhes, 31054 Toulouse Cedex, France

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