If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
A 68-year-old woman had noted gradual virilization and depression for 3 years. Examination revealed a 10-cm right pelvic mass. Plasma testosterone was substantially elevated (1,082 ng/dl), but urinary ketosteroid and ketogenic steroid excretion was normal. Laparotomy revealed a 10-cm mass that replaced the right ovary and weighed 210 g. Histologic analysis revealed a leiomyoma and proliferation of hilus cells in the periphery of the mass. The plasma testosterone decreased postoperatively to 45 ng/dl. We believe that this is the first report of an ovarian leiomyoma associated with hilus cell hyperplasia that caused virilization.
REPORT OF CASE
A 68-year-old woman was examined because of depression and nausea. She had received several courses of electro-shock therapy for depression since 1978. Generalized nausea had been present for 3 years without a history of weight loss, pain, vomiting, change in bowel habits, hepatitis, or jaundice. She had noted some loss of hair on the top of her head, a receding hairline, and increased growth of hair on her breasts and abdomen. Her voice had deepened, and she was sometimes mistaken for her husband on the telephone.
She smoked one pack of cigarettes per day. Otherwise, the findings on the elicitation of the history were normal.
On physical examination, her blood pressure was 185/90 mm Hg on one occasion and 170/100 mm Hg on another. She had coarse facial features, increased axillary hair, normal facial hair, and a male pattern of baldness. On pelvic examination, a large (10-cm) right pelvic mass was found; it was described as smooth, cystic, and semifixed. The uterus was normal sized. The patient had no clitoral hypertrophy.
Laboratory tests showed the following values: sodium 132 meq/liter, potassium 4.2 meq/liter, calcium 9.2 mg/dl, phosphate 3.6 mg/dl, glucose 87 mg/dl, total bilirubin 0.5 mg/dl, uric acid 2.6 mg/dl, and creatinine 0.9 mg/dl. The leukocyte count was 7,100/mm3, the hemoglobin concentration was 15.2 g/dl, and the platelet count was 257,000/mm3. The erythrocyte sedimentation rate was 10 mm in 1 hour. The urinalysis and urinary sediment were normal. Total thyroxine was 6.4 μg/dl, and free thyroxine was 1.3 ng/dl. Plasma corticoids were 19 μg/dl in the morning and 9.1 μg/dl in the afternoon. Plasma testosterone was 1,082 ng/dl (normal range, 20 to 80 ng/dl); free testosterone was 25.8 ng/dl (normal range, 0.3 to 1.0 ng/dl). Urinary ketosteroids were 10 mg/24 h and ketogenic steroids were 8.1 mg/24 h. Urinary estrogens were 31 μg/24 h (normal, less than 20 μg/24 h). The serum luteinizing hormone was 29.3 μg/dl (normal postmenopausal female range, 11 to 64 μg/dl), and the serum follicle-stimulating hormone was 159 μg/dl (normal range, 126 to 450 μg/dl).
The patient underwent laparotomy on June 16, 1981. A solid tumor had replaced the right ovary. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Palpation of the adrenal and renal areas bilaterally was unremarkable.
The pathology report described a leiomyoma of the right ovary which was 10 by 10 by 4.5 cm and weighed 210 g (Fig. 1). Additional sections showed a proliferation of hilus cells in the periphery of the right ovarian tumor (Fig. 2). In addition, the patient had three leiomyomas in the myometrium. The left ovary and the endometrium were atrophic.
Fig. 1Cross photograph of ovarian tumor; cut surface shows classic whorled appearance of leiomyoma.
Fig. 2Photomicrograph of ovarian tumor, illustrating subcapsular collection of hilus cells within ovarian tissue which was splayed over leiomyoma. (Hematoxylin and eosin; × 100.)
Repeat measurements of the plasma testosterone were 45 ng/dl on June 17 (the first postoperative day) and 50 ng/dl on June 19.
Unfortunately, the patient had a complicated postoperative course beginning with small bowel obstruction and infarction, then septicemia, and finally a massive cerebral infarction. She died 1 month after the operation. An autopsy revealed no other lesions that could account for the virilization; in particular, the pituitary and adrenal glands were normal.
DISCUSSION
Leiomyoma is a distinctly unusual tumor of the ovary. In contrast to the uterus and supporting ligaments, where smooth muscle is relatively abundant, the ovary itself is devoid of smooth muscle. Fallahzadeh, Dockerty, and Lee,
from our institution, reviewed the world literature up to 1972 and found 32 reported cases. They described five more cases from the Mayo Clinic during the period 1935 through 1971. In their five cases, the leiomyoma almost certainly arose from inside the ovary rather than from supporting structures, probably at the hilar area where numerous thick-walled blood vessels abound and smooth muscle could be demonstrated in the walls of the vessels. The hypothesis of a common hormonal stimulus affecting ovarian and uterine leiomyomas was proposed because a strong association seemed to exist between these two benign tumors.
None of the cases reviewed by Fallahzadeh and associates
reported three cases of ovarian leiomyoma seen in South Africa during a 10-year period. No patient described in the literature has had an ovarian leiomyoma with symptoms due to hormonal overproduction by that tumor. To our knowledge, this is the first case of an ovarian leiomyoma associated with hilus cell hyperplasia that caused virilization.
In our patient, the hilus cell hyperplasia was presumably responsible for producing the excess testosterone found in the peripheral blood and for causing the notable virilization found in the patient. Because the elevated plasma testosterone returned to normal levels within several days after the oophorectomy and hysterectomy, we believe that the hilus cell hyperplasia was the source of the testosterone overproduction and the virilization.
Hilus cell tumors of the ovary are a rare cause of defeminization and virilization. Boivin and Richart
added two further cases in 1966 and noted that patients in whom Reinke crystals could be demonstrated tended to have postmenopausal bleeding (consistent with hyperestrogenism) and patients without Reinke crystals had evidence of masculinization only. This observation has not been confirmed by other investigators.
reviewed 194 ovarian tumors that were diagnosed histologically as masculinizing ovarian tumors. In this group were 20 cases of hilus cell tumors, 75% of which were associated with clinical masculinization. They did not describe any cases of masculinization associated with an ovarian leiomyoma.
could identify only 100 cases of hilus cell tumors in the literature in a review in which they added 2 cases of their own. They noted that these tumors are usually small, unilateral, and benign. Most published cases have been associated with virilization, but several have been associated with presumed hyperestrogenism that caused hypermenorrhea or postmenopausal bleeding. Salm
made the interesting observation that in patients with pure hilus cell tumors, virilization occurred premenopausally but was absent post-menopausally, when bleeding and hyperestrogenism were more likely to occur. Our case would not fit this generalization, and, indeed, the observation is not supported by the rest of the literature.
reported peripheral vein and ovarian vein steroid measurements in two patients with proved hilus cell tumors. One of these patients had virilization, and the major end product was testosterone with minimal peripheral transformation to estrone or estradiol. In contrast, the other patient had an-drostenedione as the secretory product and a higher rate of peripheral conversion to estrone and estradiol, causing hyperestrogenism and postmenopausal bleeding rather than virilization. This report indicates that the steroid biosynthetic enzymes in hilus cell tumors may have slightly different activities and that the clinical effect of the tumor is dependent on the end product secreted, if any, and the peripheral conversion of the secreted androgens. To our knowledge, no tumor has been shown to secrete primarily estrone or estradiol.
In summary, we have reported a case of virilization occurring in a postmenopausal woman who was found to have an ovarian leiomyoma in association with a nest of hilus cell hyperplasia. In our review of the literature, we found no similar report of an ovarian leiomyoma associated with hilus cell hyperplasia that caused virilization.
REFERENCES
Fallahzadeh H
Dockerty MB
Lee RA
Leiomyoma of the ovary: report of five cases and review of the literature.
61262-2&id=gr1.jpg){kind=link}
61262-2&id=gr2.jpg){kind=link}