Two Rare Cases of Paratubal Leydig Cell Nodules: Clinical Relevance and Debated Terminology of a Noteworthy Incidentaloma.

Cells with cytologic and immunohistochemical features of Leydig cells are normally present in the ovary and the ovarian hilum, are testosterone-producing, and have been referred to as ovarian hilus cells. Rarely these cells form nests or nodules in extraovarian sites such as the mesovarium or mesosalpinx. Because they are so rare, these nodules can present a diagnostic challenge when first encountered. This report describes 2 such incidental nodules in the mesosalpinx associated with a small paratubal cyst and suggests that the term Leydig cell nodule be preferred over the nonspecific and confusing historical term ovarian hilus cell nest.

Ovarian Leydig Cell Tumor Associated with Recurrent Torsion and Virilization in an Adolescent Patient.

Ovarian tumors are rare in children; however, their incidence increases with age. Of these ovarian tumors, Leydig cell tumors are some of the rarest, accounting for less than 0.1% of all ovarian tumors across all ages. Leydig cell tumors predominantly occur in postmenopausal women and are characterized by nodular proliferation of Leydig cells in the ovarian hilum with intracytoplasmic Reinke crystals. These tumors secrete androgens, which can disrupt ovarian function, clinically presenting with abnormal uterine bleeding and virilization. Although they are generally benign, current recommendations are for treatment with a unilateral salpingo-oophorectomy. In adolescents, hyperandrogenism is most commonly caused by polycystic ovarian syndrome (PCOS); however, the differential for hyperandrogenism is broad. We present a case of a 15-year-old girl with a history of primary amenorrhea who presented with a Leydig cell tumor associated with recurrent ovarian torsion and virilization. This case reviews the challenges with diagnosis, management, and future implications of a rare androgen-secreting tumor in young patients.

Ovarian Leydig Cell Tumor and Ovarian Hyperthecosis in a Postmenopausal Woman: A Case Report and Literature Review.

Ovarian Leydig cell tumor is a rare type of ovarian steroid cell neoplasms, presenting in only 0.1% of all ovarian tumor cases, and is generally androgen-secreting and unilateral. Although they are often malignant non-spreading tumors, which have excellent prognosis, benign ovarian Leydig cell tumors with low-risk malignancy can be also detected. Ovarian hyperthecosis is a rare non-neoplastic disorder, in most cases bilateral. Ovarian tumors and ovarian hyperthecosis are one of the main causes of hyperandrogenism in postmenopausal women, a condition strongly associated with both hormonal and metabolic changes. Here, we report a 65-year-old patient with complaints of excessive body hairiness and alopecia. The laboratory investigation showed increased levels of serum testosterone and dehydroepiandrosterone sulfate (DHEA-S). Imaging, including transvaginal ultrasound and pelvic MRI revealed the presence of two masses in the ovaries. The patient underwent a laparoscopic bilateral salpingo-oophorectomy due to the ovarian tumors unknown etiology, and histopathological examination revealed a unilateral benign left ovarian Leydig cell tumor with bilateral ovarian stromal hyperplasia and ovarian hyperthecosis. Making differential diagnosis between ovarian tumors and ovarian hyperthecosis is difficult. Bilateral salpingo-oophorectomy is the treatment of choice in postmenopausal women with benign Leydig cell ovarian tumor, as well as ovarian hyperthecosis, as it offers both a cure and diagnostic confirmation.

Hyperandrogenism due to ovarian Leydig cell tumour presenting with polycythaemia.

A postmenopausal woman in her 60s was referred due to an elevated haemoglobin value found during her annual check-up. On physical examination, characteristic features of hyperandrogenism were observed which were not earlier mentioned. Laboratory investigations revealed polycythaemia accompanied by a normal erythropoietin and a negative analysis for JAK2-V617F mutation. A disproportionally and markedly elevated testosterone in combination with normal levels of adrenal androgens raised the suspicion of an ovarian source. CT scan showed nodular hyperdense lesions in both ovaries. A bilateral oophorectomy was performed and histological evaluation unfolded a Leydig cell ovarian tumour. Testosterone levels and haematological parameters normalised after surgery. Polycythaemia secondary to hyperandrogenism in postmenopausal women is an extremely rare condition and patients should be carefully analysed for the presence of androgen-secreting neoplasms. Diagnosis of the underlying pathology requires careful history, physical examination and comprehensive investigation. Treatment for this condition is surgery and resolves polycythaemia.

Testicular Lesions in Infertile Men.

OBJECTIVES: An increasing number of incidental testicular tumors are diagnosed in patients during infertility workup. The aim of this study was to evaluate the accuracy of frozen section examination (FSE) for the management of these tumors. METHODS: We retrospectively studied a series of 46 testicular tumors diagnosed during exploration for infertility from 2000 to 2019 and submitted for FSE. RESULTS: A diagnosis of malignancy was made in 23 cases on both gross examination (yellow-white or cream-colored nodules for seminomas) and FSE, then confirmed on final diagnosis in 22 of the cases. One seminoma reported on FSE was revised as being a Leydig cell tumor. The 23 other lesions were diagnosed as benign on FSE, including 11 Leydig cell tumors (yellow-brown nodules), 2 Leydig cell hyperplasias, and 10 whitish fibrous lesions. All Leydig cell lesions were confirmed except 1, which was reclassified as a Sertoli cell tumor. Of the 10 cases of fibrous lesions, 6 were associated with malignancy. CONCLUSIONS: The high incidence of Leydig cell tumors and the accuracy of FSE for these lesions demonstrate the interest in FSE. In contrast, FSE is not reliable for fibrous lesions, and surgeons should be aware that a fibrosis result often corresponds with regressed tumors.

Ovarian Leydig Cell Tumor: Cause of Virilization in a Postmenopausal Woman.

BACKGROUND Only 0.5% of all ovarian tumors are Leydig cell tumors and they are generally benign and unilateral. These androgen-secreting tumors lead to virilizing symptoms, most often in postmenopausal women. Because Leydig cell tumors are typically small, diagnosing them accurately can be challenging. CASE REPORT We report the case of a 77-year-old woman who was referred to our Endocrinology Clinic because of a 5-year history of hirsutism (Ferriman-Gallwey score of 11) with no discernible cause. The patient had high levels of serum testosterone and a normal level of dehydroepiandrosterone sulfate. Imaging, including transvaginal ultrasound and pelvic magnetic resonance, revealed a 16-mm uterine nodule, which was suspected to be a submucous leiomyoma, but no adrenal or ovarian lesions. Despite the lack of findings on imaging and because of the high suspicion for an androgen-secreting ovarian tumor, bilateral laparoscopic oophorectomy was performed. Histological examination of the specimen revealed a non-hilar Leydig cell tumor that measured 8 mm in its largest axis. After the surgery, the patient had significant clinical improvement and her laboratory test results normalized. Her sister had the same symptoms and laboratory findings at a similar age, which raised the suspicion of a possible familial genetic syndrome. No genetic testing was performed, however, because the patient's sister declined further diagnostic investigation. CONCLUSIONS Leydig cell tumors are rare, and even when they are small, they can cause symptoms related to androgen excess. As a result, diagnosing them often is challenging.

Occult symptomatic bilateral pure Leydig cell tumors in a postmenopausal woman: a case report.

BACKGROUND: Pure Leydig cell tumors (LCTs) represent 0.1% of ovarian masses. Postmenopausal patients typically present with virilization. Although LCTs can be challenging to locate on conventional imaging, positron emission tomography (PET) has been demonstrated to be effective. CASE: A 64-year-old postmenopausal woman presented with alopecia, facial hirsutism, and clitoromegaly. Laboratory findings included elevated testosterone and androstenedione. Ultrasound, computed tomography, and magnetic resonance imaging showed no adnexal masses. PET did not demonstrate ovarian fludeoxyglucose-avidity. Histopathology after bilateral salpingo-oophorectomy revealed bilateral Leydig cell tumors. Her testosterone normalized 2 weeks postoperatively. CONCLUSION: We describe the occult, symptomatic, bilateral ovarian Leydig cell tumors, an occurrence that has not been described in the literature. Virilizing tumors must be considered in patients with evidence of hyperandrogenism, even without pelvic masses on imaging.

Ovarian Leydig cell tumor and postmenopausal hirsutism with signs of virilisation.

A 71-year-old woman was referred to the endocrinology clinic to investigate postmenopausal hirsutism with 10 years of evolution. She had history of regular menses and menopause with 50 years old. Physical examination showed a male pattern facies, deepening of the voice, androgenic alopecia and hirsutism with a score of 23 according to the modified Ferriman-Gallwey scale. Testosterone and androstenedione were increased. Transvaginal ultrasound, abdominal and pelvic CT showed uterine fibroids with no pathological findings in the adrenals or ovaries. Since she had postmenopausal vaginal bleeding, uterine fibroids and suspicion of an ovarian source for her hyperandrogenism, total hysterectomy and bilateral oophorectomy were performed. Histopathological diagnosis was a Leydig cell tumour located in left ovary and endometrial carcinoma. Improvement of hirsutism was started to notice 1 month after the surgery and she was referred to the oncology clinic for adjuvant treatment.

[Leydig Cell Tumor in a Patient with Contralateral Cryptorchidism: A Rare Association]. / Tumor de Células de Leydig num Doente com Criptorquidia Contralateral: Uma Associação Rara.

Gynecomastia is a frequent sign that may be physiological or caused by various benign or malignant diseases. In rare cases, it may be caused by testicular tumors. We describe a case of progressive gynecomastia at age 20 due to a Leydig cell tumor of the right testicle in a patient with a previous history of left-sided cryptorchidism. The patient underwent orchidectomy and testicular prosthesis placement, with subsequent improvement of gynecomastia and normalization of estrogen. Our case, in addition to demonstrating that gynecomastia may regress if the underlying cause is treated in a timely manner, shows that cryptorchidism may be related with the development of Leydig cell tumors in the same way as it is in other testicular tumors.

A ginecomastia é um sinal frequente que pode ser fisiológica ou causada por várias doenças benignas ou malignas. Em casos raros pode ser originada por tumores testiculares. Nós descrevemos um caso de ginecomastia de início rapidamente progressivo aos 20 anos por um tumor de células de Leydig do testículo direito em doente com história pregressa de criptorquidia esquerda. O doente foi submetido a orquidectomia e colocação de prótese testicular assistindo-se a melhoria da ginecomastia e normalização dos valores de estrogénio. O nosso caso, além de demonstrar que a ginecomastia pode regredir se a causa subjacente for tratada atempadamente, mostra que a criptorquidia poderá estar associada ao aparecimento de tumores de células de Leydig à semelhança do que acontece com outros tumores testiculares.

Hyperandrogenism caused by ovarian Leydig cell tumour: finding the needle in a haystack.

Leydig cell tumours (LCTs) of the ovary are rare ovarian tumours that usually present with hyperandrogenism. Conventional radiological imagings are helpful in localising these tumours. However, some tumours may be too small to be localised before curative surgical removal. It is important to identify these androgen-secreting neoplasms which originate mostly from adrenals or ovaries because they are potentially malignant and require specific treatment. When conventional imagings are unrevealing, selective ovarian and adrenal venous sampling (SOAVS) is the next option. We report a case of LCT that was localised by SOAVS after results from other imaging modalities remained inconclusive.

Bilateral microscopic Leydig cell ovarian tumors in the postmenopausal woman.

A 64-year-old postmenopausal female patient presented with approximately 5 years of intermittent spotting, progressive hirsutism and significantly increased libido and clitoral hypersensitivity with spontaneous orgasms multiple times a day beginning a few months prior. Initial hormone work-up revealed elevated total serum testosterone, androstenedione and 17-hydroxyprogesterone. Luteinising hormone, follicle stimulating hormone, estradiol, dehydroepiandrosterone-sulfate, thyroid stimulating hormone and prolactin were all within normal limits. Initial suspicions suggested an androgen-secreting tumour, likely in the ovary. The lesion was undetectable on transvaginal ultrasound and abdominal-pelvic CT scan. Laparoscopic bilateral salpingo-oophorectomy was performed to remove the likely source of excess androgens. Visible gross lesions were not observed intraoperatively; however, bilateral Leydig (hilus cell) tumours were confirmed by histopathology. Serum testosterone, androstenedione and 17-hydroxyprogesterone levels were normalised postoperatively within 2 weeks and 1 month, respectively.

Leydig cell tumor of a testis with azoospermia: A case report and literature review.

RATIONALE: Testicular tumors represent 1% to 1.5% of all tumors in men. Those derived from Leydig cells are rare and account for 1% of testicular tumors. Leydig tumor cells can produce steroid hormones such as estrogen, progesterone and testosterone. The amount and type of hormones secreted by these tumors may produce complicated clinical characteristics in these patients. PATIENT CONCERNS: Here, we report a patient with azoospermia, a testicular Leydig cell tumor (LCT), and elevated plasma testosterone levels. We describe the diagnostic and therapeutic experience of this case, and our follow-up of the patient's clinical indicators and fertility status. DIAGNOSIS: The patient was diagnosed with azoospermia and a testicular LCT. INTERVENTIONS: The patient underwent testicular tumor removal and long-term follow-up. OUTCOMES: After 4 months of follow-up, the patient's semen examination index significantly improved and his wife became naturally pregnant. At 4 months of gestation, the fetus was delivered because of a ruptured amniotic cavity. Twenty-six months after tumor removal, the patient's sex hormone levels had completely returned to normal and spermatogenic function had partially recovered, but there was no natural pregnancy with his partner. CONCLUSION: For LCTs, testis sparing surgery may provide a safe and feasible option to restore spermatogenic function, although longer-term follow-up is required. Drug assistance may be required to maintain spermatogenic function and achieve fertility, and further research is required.

Tumor ovárico de células de Leydig en una niña de 7 años que se presentó como pubarquia precoz con elevación de 17 hidroxiprogesterona / Ovarian tumor of Leydig cells in a 7-year-old girl who presented as precocious pubarche with elevation of 17 hydroxyprogesterone

Clinical case: a girl of 7 ½ years who consulted for early pubarche without thelark, with a percentile size of 75 for a genetic target size in the 10th percentile, overweight with a 90th percentile BMI, and normal blood pressure. The biochemical study showed high levels of androgens: testosterone: 7.2 ng/dL, androstenedione of 5.1 ng / ml, 17OHP: 15 ng / dL with low normal DHEAS (0.26 ug/ml), Plasma Renin Activity normal low: 0.22 ng/mL/h. Initial imaging study showed a bone age of 10 years 6 months and normal abdominal and pelvic ultrasound. Molecular study showed no pathogenic variants in the CYP21A2 gene (21 Hydroxylase). With a probable diagnosis of non-classical congenital adrenal hyperplasia (HSRNC) and no known mutation, he started treatment with hydrocortisone (12 mg/m2). At 8.7 years, pubertal development begins and braking begins with LHRH analogues, which are administered for 18 months. Despite the treatment, signs of virilization and elevation of androgens (testosterone up to 130 ng/ml) are progressively accentuated, which do not diminish when trying different corticosteroid schemes. MRI of the abdomen and pelvis shows the normal adrenal glands and a solid nodular image of 2.1 x 1.6 cm in the right ovary (Figure 2), later demonstrated with pelvic ultrasound (Figure 2). Right laparoscopic oophorectomy was performed, whose biopsy demonstrated a Leydig cell tumor. One month after surgery, all androgenic levels were normalized, so the gradual suspension of corticosteroids began. Conclusion: Although HSRNC is the most frequent pathological cause of early pubarche, when it is associated with progressive clinical and biochemical hyperandrogenism despite adequate treatment and without pathogenic variants in the CYP21A2 gene, even with high levels of 17OHP, other causes should be considered, specifically, androgen producing tumors.

Caso clínico: niña de 7½ años que consulta por pubarquia precoz sin telarquia, con talla en percentil 75 para una talla objetivo genético en percentil 10, sobrepeso con IMC percentil 90 y presión arterial normal. El estudio bioquímico mostró niveles elevados de andrógenos: testosterona: 7,2 ng/dL, androstenediona de 5,1 ng/ml, 17OHP: 15 ng/dL con DHEAS normal baja (0,26 ug/ml), Actividad de Renina Plasmática normal baja: 0.22 ng/ mL/h. Estudio de imágenes inicial mostró una edad ósea de 10 años 6 meses y ecografía abdominal y pelviana normales. Estudio molecular no mostró variantes patogénicas en el gen CYP21A2 (21 Hidroxilasa). Con diagnosticó probable de hiperplasia suprarrenal congénita no clásica (HSRNC) y sin mutación conocida,inició el tratamiento con hidrocortisona (12 mg/m2). A los 8.7 años comienza desarrollo puberal y se inicia frenación con análogos de LHRH, los cuales se administran por 18 meses. A pesar del tratamiento se acentúan progresivamente los signos de virilización y hayelevación de los andrógenos (testosterona hasta 130 ng/ml), que no disminuyen intentando diferentes esquemas de corticoides. Se realiza RM de abdomen y pelvis que muestra las glándulas suprarrenales normales y una imagen nodular sólida de 2.1 x 1.6 cm en el ovario derecho (Figura 2), demostrada posteriormente con Ecografía pelviana (Figura 2). Se realiza ooforectomía derecha por vía laparoscópica, cuya biopsia demostró un tumor de células de Leydig. Un mes después de la cirugía, se normalizan todos los niveles androgénicos por lo que se inició la suspensión gradual de los corticoides. Conclusión: Aunque la HSRNC es la causa patológica más frecuente de la pubarquia precoz, cuando se asocia con un hiperandrogenismo clínico y bioquímico progresivo a pesar de un tratamiento adecuado y sin variantes patógenicas en el gen CYP21A2, incluso con niveles elevados de 17OHP, otras causas deben ser consideradas, específicamente tumores productores de andrógenos.

Mitotane treatment in patients with metastatic testicular Leydig cell tumor associated with severe androgen excess.

Mitotane (o,p'DDD) is established in the adjuvant and advanced-stage treatment of adrenocortical carcinoma and counteracts both tumor growth and tumor-related steroid production. Both the adrenal glands and the gonads are steroidogenically active organs and share a common embryogenic origin. Here, we describe the effects of mitotane in two patients with metastatic Leydig cell tumor (LCT) of the testes and associated severe androgen excess (serum testosterone 93 and 88 nmol/L, respectively; male reference range 7-27 nmol/L). Both men suffered from severe restlessness, insomnia and irritability, which they described as intolerable and disrupting normal life activities. Urinary steroid profiling by gas chromatography-mass spectrometry (GC-MS) confirmed excess androgen production and revealed concurrent overproduction of glucocorticoids and glucocorticoid precursors, which under physiological conditions are produced only by the adrenal glands but not by the gonads. In a palliative approach, they were commenced on mitotane, which achieved swift control of the hormone excess and the debilitating clinical symptoms, restoring normal quality of life. GC-MS demonstrated normalization of steroid production and decreased 5α-reductase activity, resulting in decreased androgen activation, and imaging demonstrated disease stabilization for 4-10 months. In conclusion, mitotane can be highly effective in controlling steroid excess in metastatic LCTs, with anti-tumor activity in some cases.