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

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.