Endocrine Abstracts

Background: Leydig cell ovarian tumors (LCOT) represent a rare type of sex-cord stromal tumors accounting for less than 0.1% of all ovarian tumors. (1) Although rarely described in young, LCOT most commonly occur in postmenopausal women (2). The prominent clinical features of LCOT are rapidly progressive virilization, recently described, secondary erythrocytosis and OSA (3). Suppressed plasma leptin has also been reported in patients with LCOT (4), however direct correlation of leptin with testosterone level is still debatable.

Clinical case: A 42-year old woman, presented for evaluation of hirsutism. Past medical history was significant for hypothyroidism, type 2 DM, obesity class II, OSA and secondary amenorrhea that started after the birth of her child at age 20. Previous biochemical studies demonstrated elevated testosterone leading to diagnosis of PCOS. Physical examination showed virilization, frontal alopecia, facial plethora, laryngeal hypertrophy, hirsutism (Ferriman-Gallwey score of 35), truncal obesity, acanthosis nigricans, and clitoromegaly. Laboratory studies revealed elevated total testosterone of 1242 ng/dl (< 70 ng/dl), low normal estradiol of 40.6 pg/ml (11.0–462.1 pg/ml), suppressed LH and FSH, normal prolactin, 17-OH progesterone, 24 urine free cortisol, DHEA-S, and TSH. The patient had marked erythrocytosis (Hgb of 18.3 g/dl (11.2–15.7 g/dl) and hematocrit >53% (34.1–44.9%), and significant insulin resistance (>100 units of insulin a day and four other oral hypoglycemics; HOMA-IR 11.2). Furthermore, she had elevated fasting serum insulin of 57.1 uIU/ml (normal:2.6–24.9 uIU/ml), HgbA1C 9.7%, and suppressed serum leptin level of 4.2 ng/ml (14.1–78.4 ng/ml). Pelvic ultrasound and CT of abdomen and pelvis with intravenous contrast did not reveal an adrenal adenoma or pelvic mass. Ovarian vein sampling was considered, however patient elected for TAH-BSO. Intra-operatively, both ovaries were normal in appearance. Pathology revealed 3.4 cm right ovarian pure Leydig cell tumor. Postoperatively, serum testosterone, Hgb/Hct levels rapidly normalized. Nine months after the surgery, plasma leptin increased to 39.7 ng/ml (22–121 ng/ml).

Conclusion: Secondary erythrocytosis and OSA in premenopausal women, when associated with markedly elevated testosterone levels, warrant further investigation and a high degree of suspicion for LCOT. Furthermore, in this case study, we re-demonstrated that extremely high testosterone has a suppressive effect on leptin production, as reflected by circulating levels of this hormone, which normalized following the resection of the tumor, without significant changes in BMI. The mechanism of this effect remains to be elucidated.