Virilization Secondary to an Ovarian Leydig Cell Tumor

Abstract A 60-year-old female presented with a three-year history of virilizing symptoms including facial hirsutism and deepening of voice. Her medical history was significant for renal transplantation with immunosuppressive therapy consisting of mycophenolate, cyclosporine, and low-dose prednisone. She was noted to have temporal balding and darkly pigmented terminal hair on the upper lip, cheeks, chin, shoulders, and sternum. Pelvic examination revealed clitoromegaly. Menarche occurred at age 12 with regular menstrual cycles until menopause which occurred at age 50. She had two pregnancies: a miscarriage followed by a successful pregnancy. Labs revealed an elevated total testosterone of 530 ng/dL (< 60 ng/dL), free testosterone 14.8 ng/dL (<0.87 ng/dL), androstenedione 2140 ng/dL (<200 ng/dL), and 17-hydroxyprogesterone 704 ng/dL (<285 ng/dL). LH, FSH, and estradiol were inappropriately normal in this post-menopausal female. Prolactin, TSH, DHEA-S, IGF-1 were within normal limits. Transvaginal ultrasound found a 2 cm hypoechoic right ovarian mass which was confirmed on MRI. MRI also revealed a 5 mm right adrenal nodule. Tumor markers including CA-125, Inhibin A, Inhibin B, HCG, and AFP were within normal limits. Dexamethasone suppression testing did not lower the testosterone level. 17-hydroxyprogesterone level after cosyntropin stimulation testing was 704 ng/dL (<1000 ng/dL). The patient underwent laparoscopic bilateral oophorectomy and salpingectomy, pelvic washout and omental biopsy. Pathology was consistent with a benign Leydig cell tumor. Following oophorectomy there was complete normalization of the total testosterone level (15 ng/dL, n< 60 ng/dL). A thorough history and physical exam is vital in determining the cause of hirsutism. Medications, including over-the-counter and herbal formulations should be carefully reviewed. Although cyclosporine has been associated with hirsutism, patients typically present with vellus hair formation in the affected areas rather than darkly pigmented terminal hair. In this case, hirsutism progressively worsened following menopause and physical examination was significant for virilization. Hirsutism in a combination with virilization is typically neoplastic in nature. Endogenous androgen production can originate from either the adrenal glands or ovaries. In our patient, with workup showing both ovarian and adrenal as potential sources of endogenous androgen production, an adrenal cause was excluded due to a normal DHEA-S level at baseline and a lack of suppression of testosterone after dexamethasone suppression testing. As a result, the source was localized to the ovary. While excessive androgen production resulting in virilization is seen with ovarian tumors, Leydig stromal cell tumors are extremely rare and account for less than 0.1% of all ovarian tumors.

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Case Report: Exceptional Association of Leydig Cell Ovarian Tumor and Primary Hyperparathyroidism in a Postmenopausal Patient

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.2031 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A993-A993

Author(s):

Elias Chuki ◽

Zeina Carolina Hannoush

Keyword(s):

Primary Hyperparathyroidism ◽

Leydig Cell ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Total Testosterone ◽

Pathology Report ◽

Cancer Type ◽

Imaging Studies ◽

Normal Limits ◽

Patient Reported

Abstract Background: Leydig cell tumors account for less than 0.1% of all ovarian tumors and are usually unilateral and benign. They present mostly in postmenopausal women with symptoms of hyperandrogenism. On the other hand, primary hyperparathyroidism (PHPT) is a relatively common endocrine disorder, with a prevalence of one to seven cases per 1,000 adults. It most commonly presents as an isolated, sporadic clinical entity, but in approximately 10% of the cases, it presents with a clear hereditary pattern and sometimes in association with other hormone producing tumors. Clinical Case: a 55-year-old nulliparous postmenopausal woman with history of breast cancer, Type 2 Diabetes Mellitus, hypothyroidism, hypercalcemia and hypertension who presented with progressive hirsutism and male pattern hair loss. Total testosterone levels were found to be significantly elevated in the 800s ng/dL (normal range 14–76 ng/dL). Additionally, patient was found to have mild hypercalcemia with inappropriately normal PTH and hypercalciuria, consistent with primary hyperparathyroidism (PHPT). A hypoechoic lesion in the left ovary was evident on pelvic ultrasound after 1 year of repeat imaging studies, including MRI. Bone density was within normal limits. The patient underwent bilateral Hysterosalpingo-oophorectomy and pathology report was consistent with Ovarian Leydig cell tumor. During the postoperative period, the patient reported improvement of hyperandrogenism symptoms. Discussion: We are presenting this case because of the rare association of ovarian Leydig cell tumor and PHPT in a postmenopausal female patient with virilizing symptoms. Thus, this would be the second case reported in literature by this time. This could be a rare coincidence or part of an inherited or sporadic mutation yet to be discovered. This case restates the concept that in the presence of hirsutism, rare etiologies should be sought. Virilizing tumors of the ovary should be considered despite negative initial imaging studies. PHPT should be considered in patients with asymptomatic hypercalcemia with inappropriately normal PTH and hypercalciuria. Conclusion: Careful identification and report of cases with unusual clinical presentations is essential to better understand the pathophysiology of uncommon diseases and ultimately be able to guide their management.

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Virilising ovarian tumors: a single-center experience

Endocrine Connections ◽

10.1530/ec-18-0360 ◽

2018 ◽

Vol 7 (12) ◽

pp. 1362-1369

Author(s):

Manjeetkaur Sehemby ◽

Prachi Bansal ◽

Vijaya Sarathi ◽

Ashwini Kolhe ◽

Kanchan Kothari ◽

...

Keyword(s):

Leydig Cell ◽

Serum Testosterone ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Ovarian Tumors ◽

Reproductive Age ◽

Primary Amenorrhea ◽

Total Testosterone ◽

Western India ◽

Duration Of Symptoms

Literature on virilising ovarian tumors (VOTs) is limited to case reports and series reporting single pathological type. We have analyzed the clinical, hormonal, radiological, histological, management and outcome data of VOT. This retrospective study was conducted at a tertiary health care center from Western India. Consecutive patients with VOT presenting to our endocrine center between 2002 and 2017 were included. Our study included 13 patients of VOT. Out of 13 patients, two were postmenopausal. All patients in the reproductive age group had secondary amenorrhea except one who presented with primary amenorrhea. Modified F and G score (mFG) at presentation was 24 ± 4.3 and all patients had severe hirsutism (mFG ≥15). Change in voice (n = 11) and clitoromegaly (n = 7) were the other most common virilising symptoms. Duration of symptoms varied from 4 to 48 months. Median serum total testosterone level at presentation was 5.6 ng/mL with severe hyperandrogenemia (serum testosterone ≥2 ng/mL) but unsuppressed gonadotropins in all patients. Transabdominal ultrasonography (TAS) detected VOT in all except one. Ten patients underwent unilateral salpingo-oophorectomy whereas three patients (peri- or postmenopausal) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Seven patients had Sertoli Leydig cell tumor, three had steroid cell tumor and two had Leydig cell tumor and one had miscellaneous sex cord stromal tumor. All patients had normalization of serum testosterone after tumor excision. In conclusion, VOTs present with severe hyperandrogenism and hyperandrogenemia. Sertoli Leydig cell tumor is the most common histological subtype. Surgery is the treatment of choice with good surgical outcome.

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The Story of a Radiologically Undetectable, Testosterone Producing Leydig Cell Tumor

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.2131 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A1041-A1042

Author(s):

Natalie Kappus ◽

Oday Karadsheh ◽

Dhammi K K Jayathilaka ◽

Paresh Dandona

Keyword(s):

Ct Scan ◽

Histological Examination ◽

Leydig Cell ◽

Transvaginal Ultrasound ◽

Free Testosterone ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Ovarian Tumors ◽

Total Testosterone ◽

Stromal Tumors

Abstract Introduction: Leydig stromal cell tumors are uncommon ovarian tumors that produce testosterone leading to hyperandrogenism. We present a case of a 63 year old lady with significantly elevated testosterone levels that did not have clear ovaries visualized on imaging, but was subsequently found to have a Leydig cell tumor on pathology after ovarian resection. Clinical Case: A 63 year old female with a past medical history of COPD, hypothyroidism, hyperlipidemia, hypertension and uterine fibroids status post hysterectomy and left oophorectomy in 1995 was referred to endocrinology for hirsutism. The patient reported first noticing abnormal hair growth approximately one year prior to presentation having developed increasingly coarse and thick facial hair, abdominal wall hair, and chest hair. On physical examination, she was noted to have coarse hair across her upper lip and chin continuous along the jawline along with fine, dark hair diffusely across her anterior abdomen. Initial laboratory cell evaluation revealed total testosterone 378 ng/dL, free testosterone 53ng/dL, DHEAS 64 ug/dL. Repeat labs drawn three months later confirmed the markedly elevated total testosterone of 362 ng/dL and free testosterone 44.2 ng/dL, concentrations normally seen in males. A CT scan of the abdomen and pelvis was done and did not reveal any masses. In addition, no ovaries were appreciated on imaging. A transvaginal ultrasound also did not reveal any clear ovaries. The patient ended up undergoing a right oophorectomy. Histological examination was consistent with a Leydig cell tumor. Following oophorectomy, her testosterone concentrations normalized (5ng/dL) and hirsutism began to regress. Clinical Lesson: Hyperandrogenism in women is typically classified into non-tumorous and tumorous. The differential for non-tumorous hyperandrogenism includes PCOS, congenital adrenal hyperplasia (CAH), and ovarian hyperthecosis. Tumorous causes include ovarian tumors such as Sertoli-Leydig cell tumors, hilus cell tumors, and theca cell tumors. Adrenal tumors secreting testosterone are extremely rare. Often with these tumors, there is significantly increased testosterone levels (> 140ng/dL) and rapid progression of symptoms. Sex cord stromal tumors account for only 5-8% of all ovarian tumors with Leydig stromal tumors a rare group that accounts for less than 0.1% of all ovarian tumors. The tumors are functional producing testosterone leading to marked hyperandrogenism and virilization. They are also usually benign and unilateral. This patient had hyperandrogenism manifested by hirsutism with markedly elevated testosterone concentrations. In addition, this case is unique in that a CT scan and transvaginal ultrasound did not clearly demonstrate her right ovary. Despite having a normal appearing right ovary during surgery, patient was found to have Leydig cell tumor following histological examination.

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Ovarian Tumors and Related Lesions in Aged Chimpanzees

Veterinary Pathology ◽

10.1177/030098587701400410 ◽

1977 ◽

Vol 14 (4) ◽

pp. 380-386 ◽

Cited By ~ 18

Author(s):

C. E. Graham ◽

H. M. Mcclure

Keyword(s):

Leydig Cell ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Ovarian Tumors ◽

The Other ◽

Adenomatous Hyperplasia ◽

Well Differentiated

The ovaries of a 48-year-old chimpanzee each contained a large bilateral fibrothecoma. A 39-year-old chimpanzee had two small fibrothecomas in one ovary and a well-differentiated Sertoli-Leydig cell tumor in the other; there also was adenomatous hyperplasia of the endometrium. Both animals had extensive thecal hypertrophy in the ovaries. Thecal hypertrophy might have been a source of excessive estrogen and could have been a partial cause of the ovarian tumors.

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Diagnosis of Sertoli-Leydig Cell Tumor of the Ovary Complicated by the Pattern of Hyperandrogenemia and Results of Imaging

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1586 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A779-A780

Author(s):

Amruta Jaju ◽

Vanessa Williams ◽

Mohammad Jamal Uddin Ansari ◽

Mariam Murtaza Ali ◽

Michael G Jakoby

Keyword(s):

Postmenopausal Woman ◽

Leydig Cell ◽

Adnexal Mass ◽

Dehydroepiandrosterone Sulfate ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Total Testosterone ◽

Well Differentiated ◽

The Right ◽

Ovarian Masses

Abstract Introduction: Virilization in a postmenopausal woman requires evaluation for an androgen-secreting tumor. The differential diagnosis includes adrenal carcinomas and adenomas and Sertoli-Leydig cell tumors, granulosa-theca cell tumors, and hilus-cell tumors of the ovaries. We present a case of virilization in a postmenopausal woman caused by a Sertoli-Leydig cell tumor (SLCT) in which evaluation was complicated by the pattern of androgen elevation, bilateral adrenal nodules, and absence of an adnexal mass. Case: A 64-year-old female was referred for evaluation of hyperandrogenism. Hirsutism, temporal hairline regression, and unusually deep voice were noted on examination. Two total testosterone levels obtained one month apart were 146 ng/dL (2-45), and measurements of dehydroepiandrosterone sulfate (DHEAS) and androstenedione were 299 mcg/dL (12-133) and 1.84 ng/mL (0.130-0.820), respectively. Abdominal CT revealed bilateral adrenal nodules - 2 cm and - 5 Hounsfield units (HU) on the left, and 1.5 cm and 5 HU on the right - but no ovarian masses. Transvaginal ultrasonography also failed to identify a discrete ovarian mass but showed endometrial hyperplasia. Virilization, magnitude of testosterone elevation, and results of imaging were felt to be most strongly indicative of ovarian hyperthecosis, and the patient underwent laparoscopic bilateral salpingo-oophorectomy and hysterectomy. The right ovary was 2.3 cm in largest diameter and approximately 90% replaced by an orange-red mass that showed Sertoli and Leydig cells on microscopy, immunohistochemical staining for the sex cord proteins inhibin and calretinin, and presence of the Leydig cell marker melan A. It was classified as well differentiated. Additional CT imaging and robotic assisted laparoscopy confirmed a stage IA tumor. One month after surgery, hyperandrogenemia had completely resolved (total testosterone < 10 ng/dL, androstenedione 0.379 ng/mL, and DHEAS 99 mcg/dL), and changes of virilization had mostly regressed at an eight months appointment. Discussion: SLCTs are a type of sex-cord stromal ovarian tumor. They constitute < 0.5% of ovarian tumors but account for approximately 75% of testosterone-secreting ovarian masses. This patient’s case was unusual for multiple reasons: 1. Age - most SLCTs are diagnosed in the second or third decade, 2. Imaging - CT and ultrasonography usually show a solid or solid and cystic adnexal mass, and co-existing adrenal nodules are rare, likely due to typical young age of presentation, and 3. Pattern of androgen elevation - DHEAS was more than two-fold elevated, and usually < 10% of DHEA and DHEAS are produced by the ovaries. However, DHEAS fell significantly after oophorectomy. SLCTs are a potential etiology of virilization in postmenopausal women even in the absence of a detectable adnexal mass and when biochemistries and imaging raise the possibility of an adrenal source of androgen.

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Sertoli-Leydig cell tumour of ovary: a case report

Medical Journal of Shree Birendra Hospital ◽

10.3126/mjsbh.v10i2.6462 ◽

2012 ◽

Vol 10 (2) ◽

pp. 35-37

Author(s):

Arju Chand ◽

Rajesh Pant

Keyword(s):

Medical Journal ◽

Case Report ◽

Leydig Cell ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Ovarian Tumors ◽

Cell Tumour ◽

Leydig Cell Tumour

Sertoli–Leydig cell tumor are very rare and make up approximately 0.5% of all ovarian tumors. They typically produce androgen and clinical virilization is present in 70-85% of cases. We report of a Sertoli–Leydig cell tumor without virilization. DOI: http://dx.doi.org/10.3126/mjsbh.v10i2.6462 Medical Journal of Shree Birendra Hospital July-Dec 2011 10(2) 35-37

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Marked hyperandrogenicity in a 60-year-old woman

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-17-0075 ◽

2017 ◽

Vol 2017 ◽

Cited By ~ 1

Author(s):

Khaled Aljenaee ◽

Sulaiman Ali ◽

Seong Keat Cheah ◽

Owen MacEneaney ◽

Niall Mulligan ◽

...

Keyword(s):

Leydig Cell ◽

Testosterone Level ◽

Histopathological Examination ◽

Incidental Finding ◽

Serum Testosterone ◽

Leydig Cell Tumor ◽

Cell Tumor ◽

Serum Testosterone Level ◽

List Type ◽

Dheas Level

Markedly elevated androgen levels can lead to clinical virilization in females. Clinical features of virilization in a female patient, in association with biochemical hyperandrogenism, should prompt a search for an androgen-producing tumor, especially of ovarian or adrenal origin. We herein report the case of a 60-year-old woman of Pakistani origin who presented with the incidental finding of male pattern baldness and hirsutism. Her serum testosterone level was markedly elevated at 21 nmol/L (normal range: 0.4–1.7 nmol/L), while her DHEAS level was normal, indicating a likely ovarian source of her elevated testosterone. Subsequently, a CT abdomen-pelvis was performed, which revealed a bulky right ovary, confirmed on MRI of the pelvis as an enlarged right ovary, measuring 2.9 × 2.2 cm transaxially. A laparoscopic bilateral salpingo-oophorectomy was performed, and histopathological examination and immunohistochemistry confirmed the diagnosis of a Leydig cell tumor, a rare tumor accounting for 0.1% of ovarian tumors. Surgical resection led to normalization of testosterone levels. Learning points: Hirsutism in postmenopausal women should trigger suspicion of androgen-secreting tumor Extremely elevated testosterone level plus normal DHEAS level point toward ovarian source Leydig cell tumor is extremely rare cause of hyperandrogenicity

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