Leydig cell tumor of the testis with azoospermia and elevated delta4 androstenedione: case report
© The Author(s). 2016
Received: 29 June 2016
Accepted: 14 September 2016
Published: 8 November 2016
Secreting interstitial cell (Leydig cell) tumors are rare. In adults, the clinical picture and steroid levels are variable.
This paper presents a case of left testicular tumor, showing azoospermia with normal serum level of total testosterone, collapsed FSH and LH, and high delta4 androstenedione. Histopathological investigation revealed a Leydig cell tumor. TESE allowed spermatozoa extraction and freezing. Testicular histology found hypospermatogenesis and germ-cell aplasia with interstitial fibrosis. Surgical resection of the tumor resulted in normalization of gonadotropins and fall in serum delta4 androstenedione to subnormal levels in the postoperative period confirming that the tumor was secreting delta4 androstenedione. It was hypothesized that high delta4 androstenedione resulted in intra tumoral 17 β-HSD overtaken by delta4 androstenedione or that 17 β-HSD activity in the tumor was different from that of normal Leydig cells. Three months after surgery sperm analysis found a complete recovery of spermatogenesis. A spontaneous pregnancy occurred 3 months after surgery and a girl was born.
In this case, the diagnosis of testicular Leydig cell tumor secreting delta4 androstenedione was made in a context of azoospermia.
KeywordsAzoospermia Infertility Hormone secreting testicular tumor Leydig cell tumor delta4 androstenedione TESE
Les tumeurs testiculaires interstitielles (ou tumeurs testiculaires à cellules de Leydig) à expression endocrine sont rares. Chez l’adulte le tableau clinique et le bilan hormonal sont variables.
Présentation du cas
Cet article présente le cas d’une tumeur testiculaire gauche dans un contexte d’azoospermie. Le bilan hormonal montre des gonadotrophines effondrées, une testostéronémie normale et une delta4 androstenedione augmentée. L’examen anatomopathologique a mis en évidence une tumeur à cellule de Leydig. La TESE a permis l’extraction et la congélation de spermatozoïdes. L’histologie a retrouvé un aspect mixte d’hypospermatogenèse diminuée incomplète et d’aplasie. Dans les suites de l’orchidectomie partielle gauche les taux de gonadotrophines se sont normalisés ainsi que le taux de delta4 androstenedione. L’hypothèse physiopathologique est que l’augmentation de la delta4 androstenedione résulte de la sursaturation de la 17 β-HSD intra-tumoral ou que l’activité de la 17 β-HSD intra-tumoral est différente de celle dans les cellules de Leydig normales. Trois mois après la chirurgie, le spermogramme a montré une normalisation des paramètres spermatiques et une grossesse spontanée est survenue permettant la naissance d’une petite fille.
Dans ce cas clinique, le diagnostic de tumeur testiculaire à cellule de Leydig sécrétant de la delta4 androstenedione a été fait dans un contexte d’azoospermie.
KeywordsAzoospermia Infertility Hormone secreting testicular tumor Leydig cell tumor delta4 androstenedione TESE
Mots clésAzoospermie Infertilité Tumeur testiculaire à sécrétion endocrine Tumeur à cellules de Leydig delta4androstenedione TESE
Testicular neoplasms represent 1–1.5 % of all tumors in men. Those derived from the interstitial cells of Leydig are rare, constituting 1 % of testicular tumors. Hormone secreting interstitial cell tumors are more unusual than non-secreting interstitial tumors. In young males, the tumor is usually associated with precocious puberty , whereas in adults, the clinical picture and steroid levels are variable [2–20]. This paper reports a case of testicular Leydig cell (interstitial cell) tumor secreting delta4 androstenedione in a patient with azoospermia.
A 44 year old man was referred to our clinic for secondary infertility; he had no medical or surgical history or medical treatment. He was a butcher and married.
Under 3 months
Progressive motility (%)
Typical spermatozoa (%)
Serum level of total testosterone was 5.03 mg/L, FSH 1.0 IU/L. Spermoculture found ureaplasma urealyticum.
2014 before surgery
3 months after surgery
Normal in size and echotexture, without focal lesion; normal epididymides; no varicocele; normal vasculature at Doppler examination
Normal echotexture Volume 8.5 mL
Volume 15.7 mL
Presence of a 30 × 16 mm polylobulated intratesticular mass, with low echogenicity, numerous septa, and high vasculature at Doppler examination
Low echogenicity intratesticular lobulated mass, with heterogeneous echotexture, low echogenicity, measuring 32 × 31 × 23 mm, with slight vasculature at Doppler examination
Rearranged aspect secondary to surgery
Volume 12 mL
Right testis: Normal in size and echotexture, without a focal lesion; normal epididymides; no varicocele; normal vasculature at Doppler examination.
Left testis: a left hypoechoic polylobulated intratesticular mass measuring 30 × 16 mm, including numerous septa, and showing high vasculature at Doppler examination.
At that time, ofloxacine 200 mg twice per day during 15 days was prescribed. A spontaneaous pregnancy occurred in 2009 and a boy was born in 2010 (3800 g). Between 2009–2014 the patient had no follow-up for this mass.
In 2014 the patient consulted a doctor in our clinic as he wished to have another child. Semen analyses showed strict azoospermia with normal volume (Table 1).
Physical examination showed a normal andrological development, testes were present in the scrotum, a slightly indurated mass could be felt in the upper pole of the left testis. Right testis was hypotrophic, seminal conducts were felt. There was neither gynecomastia nor any sign of hypercortisolism.
Scrotal ultrasonography found (Table 2) a hypotrophic right testicle (8.5 mL), but a hypoechoic lobulated mass was visible in the left testicle with heterogeneous echotexture, measuring 32 × 31 × 23 mm, with slight vasculature at Doppler examination.
Hormonal results in 2014
Total testosterone ng / mL
Free testosterone pmol/L
Inhibin B pg/mL
Delta4 androstenedione ng/mL
17 OH progesterone ng/mL
Dehydroepiandrosterone Sulfate μmol/L
Human CG IU/L
Alfa foeto protein μg/L
Cortisol (8 AM) μg / 100 mL
A marked increase in androstenedione levels and suppressed gonadotropin levels were found which are likely to contribute to the failure of spermatogenesis. Normal Dehydroepiandrosterone Sulfate argues against adrenal hyperandrogenism.
Abdomen and Thorax Computed Tomography (CT) imaging were normal (no adrenal gland abnormality and no secondary lesions).
The committee on tumoral diseases agreed on the decision to perform a testis-sparing surgery with extemporaneous histological examination. We decided to perform a testicular sperm extraction (TESE) at the same time. TESE allowed spermatozoa extraction with freezing.
Selected hormonal values before and after surgery in 2014
1 month before surgery
1 day post-operative
2 months post-operative
Total Testosteronea (ng/mL)
Delta4 androstenedione (ng/mL)
Inhibin B (pg/mL)
Scrotal ultrasonography 3 months after surgery described a normal right testis which had increased in size (volume 15 mL) and a left testis with a rearranged aspect secondary to surgery (Table 2).
Three months after surgery semen analyses showed a complete recovery of spermatogenesis (Table 1). A spontaneous pregnancy occurred, 3 months after surgery and a girl was born in 2015 (3450 g).
To the authors’ knowledge only one case of androstenedione secreting testicular Leydig cell tumors associated with azoospermia has been reported previously . In that case, serum levels of testosterone, dihydrotestosterone, 5α-androstane-3α,17βdiol and oestradiol were normal and oestrone was moderately increased. In contrast androstenedione was extremely elevated. Testosterone levels in the spermatic vein were decreased indicating a partial deficiency of 17β hydroxysteroid dehydrogenase in the tumoral tissue. Twenty-eight months after surgery, all sex steroids including androstenedione were normal.
In the present case, total suppression of LH levels and almost complete suppression of FSH levels were associated with azoospermia, despite intratesticular testosterone secretion by the tumor, and azoospermia proved to be fully reversible within less than three months after tumor removal and normalization of hormone levels, which shows that normal secretion of gonadotropins, plays a major role in maintaining spermatogenesis. This appears to be in agreement with other (rare) reports of patients with Leydig cell tumors and reversible azoospermia, who did not suffer from other testicular disorders. Interestingly, in these previous reports, the patients were also found to have testosterone secreting Leydig cell tumors with undetectable  or markedly reduced  gonadotropin levels, which suggests that intratesticular secretion of testosterone by the tumor is not sufficient to prevent azoospermia in spite of marked suppression of LH and FSH secretion. The present paper shows that even with collapsed gonadotropin levels TESE allowed extraction of spermatozoa.
Hormone secreting interstitial cell tumors are rare and have variable clinical presentations. In the case presented in this paper, the diagnosis was made in a context of azoospermia. Few months after tumorectomy, sex steroid levels and spermatogenesis returned to normal and a spontaneous pregnancy occurred.
- 17 β-HSD:
17Beta hydroxysteroid dehydrogenase
Follicle stimulating hormone
Testicular sperm extraction
Availability of data and materials
JP participated to the patient care, drafted the manuscript. ALB carried out semen analyses. AD participated to draft the manuscript. CL participated to the patient care. PP participated to do magnetic resonance imaging, abdomen and thorax computed tomography and scrotal ultrasonography. FM participated to the patient surgery. XL realized histopathological investigations. VM participated to emend the manuscript, did testicular histology. JMR participated to emend the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Ethics approval and consent to participate
Consent for publication
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Turner WR, Derrick FC, Wohltmann H. Leydig cell tumor in identical twin. Urology. 1976;7(2):194–7.View ArticlePubMedGoogle Scholar
- Boulanger P, Somma M, Chevalier S, Bleau G, Roberts KD, Chapdelaine A. Elevated secretion of androstenedione in a patient with a Leydig cell tumour. Acta Endocrinol (Copenh). 1984;107(1):104–9.Google Scholar
- Kondoh N, Koh E, Nakamura M, Namiki M, Kiyohara H, Okuyama A, et al. Bilateral Leydig cell tumors and male infertility: case report. Urol Int. 1991;46(1):104–6.View ArticlePubMedGoogle Scholar
- Gabrilove JL, Nicolis GL, Mitty HA, Sohval AR. Feminizing interstitial cell tumor of the testis: personal observations and a review of the literature. Cancer. 1975;35(4):1184–202.View ArticlePubMedGoogle Scholar
- Perez C, Novoa J, Alcañiz J, Salto L, Barcelo B. Leydig cell tumour of the testis with gynaecomastia and elevated oestrogen, progesterone and prolactin levels: case report. Clin Endocrinol (Oxf). 1980;13(5):409–12.View ArticleGoogle Scholar
- Mineur P, De Cooman S, Hustin J, Verhoeven G, De Hertogh R. Feminizing testicular Leydig cell tumor: hormonal profile before and after unilateral orchidectomy. J Clin Endocrinol Metab. 1987;64(4):686–91.View ArticlePubMedGoogle Scholar
- Valensi P, Coussieu C, Kemeny JL, Attali JR, Amouroux J, Sebaoun J. Endocrine investigations in two cases of feminizing Leydig cell tumour. Acta Endocrinol (Copenh). 1987;115(3):365–72.Google Scholar
- Schwarzman MI, Russo P, Bosl GJ, Whitmore WF. Hormone-secreting metastatic interstitial cell tumor of the testis. J Urol. 1989;141(3):620–2.PubMedGoogle Scholar
- Kerlan V, Nahoul K, Abalain JH, Mangin P, Bercovici JP. Oestrogen secreting Leydig cell tumour and GnRH agonist in-vivo and in-vitro studies. Clin Endocrinol (Oxf). 1992;37(3):221–6.View ArticleGoogle Scholar
- Caron PJ, Bennet AP, Plantavid MM, Louvet JP. Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis. Eur J Endocrinol Eur Fed Endocr Soc. 1994;131(2):156–9.View ArticleGoogle Scholar
- Daniel L, Lechevallier E, Liprandi A, de Fromont M, Pellissier JF, Coulange C. Malignant Leydig cell tumor of the testis secreting progesterone. Prog En Urol J Assoc Fr Urol Société Fr Urol. 1998;8(6):1047–50.Google Scholar
- Mostafid H, Nawrocki J, Fletcher MS, Vaughan NJ, Melcher DH. Leydig cell tumour of the testis: a rare cause of male infertility. Br J Urol. 1998;81(4):651.View ArticlePubMedGoogle Scholar
- Fallick ML, Lin WW, Lipshultz LI. Leydig cell tumors presenting as azoospermia. J Urol. 1999;161(5):1571–2.View ArticlePubMedGoogle Scholar
- Hekimgil M, Altay B, Yakut BD, Soydan S, Ozyurt C, Killi R. Leydig cell tumor of the testis: comparison of histopathological and immunohistochemical features of three azoospermic cases and one malignant case. Pathol Int. 2001;51(10):792–6.View ArticlePubMedGoogle Scholar
- Markou A, Vale J, Vadgama B, Walker M, Franks S. Testicular leydig cell tumor presenting as primary infertility. Horm Athens Greece. 2002;1(4):251–4.View ArticleGoogle Scholar
- Carmignani L, Colombo R, Gadda F, Galasso G, Lania A, Palou J, et al. Conservative surgical therapy for leydig cell tumor. J Urol. 2007;178(2):507–11.View ArticlePubMedGoogle Scholar
- Sengupta S, Chatterjee U, Sarkar K, Chatterjee S, Kundu A. Leydig cell tumor: a report of two cases with unusual presentation. Indian J Pathol Microbiol. 2010;53(4):796–8.View ArticlePubMedGoogle Scholar
- Sönmez N, Ton O, Arısan S, Kılınç F, Eken K, Güney S. Bilateral Leydig cell tumor of the testis: a case report. Contemp Oncol Pozn Pol. 2012;16(4):356–9.Google Scholar
- Straume AH, Løvås K, Miletic H, Gravdal K, Lønning PE, Knappskog S. Elevated levels of the steroidogenic factor 1 are associated with over-expression of CYP19 in an oestrogen-producing testicular Leydig cell tumour. Eur J Endocrinol Eur Fed Endocr Soc. 2012;166(5):941–9.View ArticleGoogle Scholar
- Maqdasy S, Bogenmann L, Batisse-Lignier M, Roche B, Franck F, Desbiez F, et al. Leydig cell tumor in a patient with 49, XXXXY karyotype: a review of literature. Reprod Biol Endocrinol RBE. 2015;13:72.View ArticleGoogle Scholar
- Kumar A, Shekhar S, Dhole B. Thyroid and male reproduction. Indian J Endocrinol Metab. 2014;18(1):23–31.View ArticlePubMedPubMed CentralGoogle Scholar