Hypothyroidism and Hyperlipidemia With a Virilizing Ovarian Steroid Cell Tumor, Not Otherwise Specified
By Tsai, Horng-Jyh; Chen, Shu-Chen; Wei, Hsiao-Yun; Chen, Gin-Den
Abstract
Steroid cell tumors, not otherwise specified, are rare ovarian sex cord-stromal tumors with malignant potential. The majority of these tumors produce steroids, with testosterone being the most common. A 44-year-old woman with hypothyroidism and hyperlipidemia presented with abrupt onset of oligomenorrhea, progressive virilization as acne, hirsutism and clitoromegaly, and a non- palpable pelvic mass. The preoperatively elevated serum testosterone level returned to normal after salpingooophorectomy, and then menstrual flow became regular.
Keywords: Steroid cell tumors (not otherwise specified), virilizing ovarian tumor, hypothyroidism, hyperlipidemia
Introduction
Steroid cell tumors, not otherwise specified (NOS), are rare ovarian sex cord-stromal tumors. The majority of these tumors produce hormones, with testosterone being the most common [1]. This report describes the case of an adult woman with hypothyroidism and hyperlipidemia, who presented with abrupt onset of oligomenorrhea, progressive virilization and a non-palpable benign steroid cell tumor, NOS. The elevated serum levels of testosterone returned to normal after surgery.
Case report
A 44-year-old Taiwanese housewife, G3P3, had a 15-year history of hypothyroidism (serum thyroid-stimulating hormone (TSH): 232.8 mU/ 1, reference value, 0.4-5.0 mU/1; thyroxine: 1.12 g/ml, reference value, 4.5-12.0 g/ml; triiodothyronine: normal) under fair control with thyroxine. Hyperlipidemia (serum cholesterol: 430 mg/dl, reference value, 15-150 mg/dl; serum triglycerides: 376 mg/dl, reference value, 110-250 mg/dl; high-density lipoprotein cholesterol: normal) developed 8 years prior to the presentation. Various lipid-lowering drugs had been prescribed and achieved fair control in the last few years. Abrupt onset of oligomenorrhea developed 4 months prior to this presentation, and gradual virilization as development of acne, increasing facial and pubic hair, and voice hoarseness for 3 months. Past medical history revealed trivial mitral valve regurgitation with slight limitation of physical activity. She was 162 cm in height and 69.5 kg in weight. Acne was prominent. The thyroid gland was normal. Pelvic examination revealed normal external genitalia but a mildly enlarged clitoris, 12 mm in width. The right adnexal fullness felt without a palpable tumor.
Laboratory analyses showed normal blood counts, and normal serum values of carcinoembryonic antigen and follicle-stimulating hormone. Serum total testosterone level was 8.4 ng/ml (reference value, 0.06- 0.86 ng/ml). Transvaginal ultrasound identified a well- circumscribed, tabulated, solid right ovarian tumor, 4.5 cm 4.0 cm in diameter (Figure 1). Morphological index [2] of this tumor was 2. Tumor vessels presented a flow pulsatility index of 0.77 and a resistance index of 0.54 in the Doppler study. No ascites or other abnormalities were present. She underwent laparoscopic salpingooophorectomy.
Figure 1. Transvaginal ultrasound image of steroid cell tumor, not otherwise specified, identifying a well-circumscribed, tabulated, solid right ovarian tumor (arrows), 4.0 cm 3.8 cm in diameter.
Figure 2. Gross section appearance of steroid cell tumor, not otherwise specified, of the right ovary showing a yellow-orange, solid, well-demarcated typical tumor, 4.5 cm 3.7 cm in diameter.
Figure 3. Microscopic appearance of steroid cell tumor, not otherwise specified, showing large aggregates of typical polygonal to round tumor cells having distinct cell borders, central nuclei, prominent nucleoli and moderate to abundant spongy or eosinophilic granular cytoplasm, intersected by delicate fibrous bands (hematoxylin and eosin staining, 400).
Gross pathological examination of the ovary revealed a typical yellow-orange solid mass, 4.5 cm 4.0 cm 3.5 cm in diameter (Figure 2). Microscopically, the findings were consistent with a benign ovarian steroid cell tumor, NOS (Figure 3).
Postoperatively, the serum testosterone level returned to normal, and the serum level of dehydroepiandrosterone sulfate was normal. Then the menstrual flow became regular a week after the operation. Acne disappeared spontaneously.
Discussion
More than 100 cases of lipoid cell tumors have been reported. This nomenclature is misleading because some tumors have little or no lipid present. Scully initiated the term ‘steroid cell tumor of the ovary’ in 1979. This term more accurately describes the morphological appearance of these tumors and provides insight into their clinical manifestations. There are three steroid cell tumor subtypes: steroid cell tumor (NOS), stromal luteoma and Leydig cell tumor. Steroid cell tumors, NOS account for approximately 60% of steroid cell tumors and are associated with androgenic changes in approximately half of cases [3,4]. Steroid cell tumors, NOS typically are solid and well-circumscribed, occasionally lobulated, and rarely bilateral. These tumors are composed of two similar- appearing polygonal cell types that differ only in their cytoplasmic appearance (eosinophilic vs. vacuolated).
In 1987, Hayes and Scully reported the largest series of patients (n = 63) with steroid cell tumor, NOS [I]. The most common initial manifestation was virilization (41%). In 24 cases, the tumor was designated probably benign. Steroid cell tumor, NOS sometimes produce hormones other than testosterone; for example, estradiol secretion in 6-23% of patients. These tumors have been associated with Cushing’s syndrome in 6-10% of cases [I]. In general, the degree of TSH elevation correlates with the clinical severity in patients with hypothyroidism. Our patient was under fair control of her thyroid dysfunction, therefore a few nonspecific symptoms of hypothyroidism were encountered. In a MEDLINE literature search from 1966 to 2006 using search terms ‘hypothyroidism, or hyperlipidemia’ and Ovarian neoplasm, or ovarian sex cord-stromal tumors, or ovarian steroid cell tumor, or lipoid cell tumor, or lipid cell tumor’, we were unable to find any cases of hypothyroidism and ovarian steroid cell tumor. A PubMed literature search yielded the same result.
The diagnosis of these rare tumors can be problematic especially in the case of a non-palpable ovarian tumor. Careful history-taking can eliminate medications as a cause of virilization and hirsutism. Current medications prescribed for our patient could not be a cause of her clinical scenario. Development of defeminization followed by virilization can be a helpful sign for diagnosis. The preoperative evaluation for women with virilization includes a bimanual examination, serum testosterone and dehydroepiandrosterone sulfate, and computed tomography (CT) of the adrenals and ovaries [5]. The radiological (magnetic resonance imaging) features of steroid cell tumor, NOS of the right ovary with metastasis to the uterus were first presented in the literature in 1998 [4]. Although CT can identify an adrenal mass as small as 1.5 cm, transabdominal and transvaginal ultrasound scans are very useful in evaluating ovarian tumor size and morphology [6]. Monteagudo and colleagues concluded that gray-scale transvaginal sonography combined with color Doppler studies can make the diagnosis of small steroid cell tumor easier and, at times, better than costly imaging modalities [7]. It is really a rare clinical scenario if a steroid cell tumor, NOS develops in an accessory ovary (an uncommon congenital anomaly of the female reproductive tract) and attaches to the infundibulum of the fallopian tube [8].
The differential diagnosis of raised serum testosterone levels includes functional adrenal hypersecretion and an androgen- producing neoplasm. Elevated serum testosterone levels are commonly associated with ovarian tumors, while increased dehydroepiandrosterone sulfate levels are often associated with adrenal tumors [5]. In the differential diagnosis of young adult women with secondary amenorrhea, or in the differential diagnosis of severe hyperandrogenism and virilization even in perimenopausal women, Leydig cell tumor of the ovary should also be considered [9,1O].
Differential diagnosis would include other sex cord-stromal tumors, primary and metastatic carcinomas, and melanomas. Of the different markers that have been reported to stain these tumors, inhibin has proved to be the most helpful, because most steroid cell tumors express this marker [U]. Also, recent reports have suggested that immunostaining with calretinin is a sensitive marker for steroid cell tumors, NOS. Epithelial membrane antigen is of particular utility for distinguishing ovarian clear cell carcinoma and renal clear cell carcinoma from steroid cell tumors, since most carcinomas express epithelial membrane antigen, while most steroid cell tumors do not [12].
The biochemical characteristics of our patient were typical of an ovarian neoplasm. A typical ultrasonogram in preoperative assessment of this nonpalpable tumor was demonstrated. The characteristic gross section and typical microscopic appearance of this tumor are shown herein. The management of steroid cell tumors, NOS is, like for other ovarian stromal tumors, surgical – including conservative surgery to complete surgical staging. Postoperative follow-up should include monitoring of hormone levels. Therapy should be individualized based on tumor \histology, surgical staging, and the desire for future childbearing. It is well known that gonadotropin- releasing hormone agonist (GnRHa) suppresses elevated androgen levels in patients with Leydig cell tumor, etc. GnRH-a may be an alternative choice to be considered as adjuvant therapy for postoperative management of a persistent or recurrent hormone- producing steroid cell tumor of the ovary [13].
References
1. Hayes MC, Scully RE. Ovarian steroid cell tumor (not otherwise specified): a clinicopathological analysis of 63 cases. Am J Surg Pathol 1987; 11:835-845.
2. Ueland FR, DePriest PD, Pavlik EJ, Kryscio RJ, van Nagell JR Jr. Preoperative differentiation of malignant from benign ovarian tumors: the efficacy of morphology indexing and Doppler flow sonography. Gynecol Oncol 2003;91:46-50.
3. Young RH, Path FRC, Scully RE. Sex cord-stromal, steroid cell, and other ovarian tumors with endocrine, paraendocrine, and paraneoplasn’c manifestations. In: Kurman RJ, editor. Blaustein’s pathology of the female genital tract. New York: Springer-Verlag; 1994. pp 783-847.
4. Wang PH, Chao HT, Lee RC, Lai CR, Lee WL, Kwok CF, Yuan CC, Ng HT. Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis – a case report. Eur J Radiol 1998;26:269-273.
5. Surrey ES, de Ziegler D, Gambone JC, Judd HL. Preoperative localization of androgen-secreting tumors: clinical, endocrinologie, and radiologie evaluation of ten patients. Am J Obstet Gynecol 1988;158:1313-1322.
6. Outwater EK, Marchetto B, Wagner BJ. Virilizing tumor of the ovary: imaging features. Ultrasound Obstet Gynecol 2000; 15:365- 371.
7. Monteagudo A, Heller D, Husami N, Levine RU, McCaffrey R, Timor-Tritsch IE. Ovarian steroid cell tumors: sonographic characteristics. Ultrasound Obstet Gynecol 1997;10:282-288.
8. Liu AX, Sun J, Shao WQ, Jin HM, Song WQ. Steroid cell tumors, not otherwise specified (NOS), in an accessory ovary: a case report and literature review. Gynecol Oncol 2005;97:260-262.
9. Elbadrawy M, Davies N. secondary amenorrhoea due to Leydig cell tumour. J Obstet Gynaecol 2005;25:529-530.
10. Nardo LG, Ray DW, Laing I, Williams C, McVey RJ, Seif MW. Ovarian Leydig cell tumor in a peri-menopausal woman with severe hyperandrogenism and virilization. Gynecol Endocrinol 2005;21:238- 241.
11. Mohanty A, Trujillo YP. Virilization and left adnexal mass in a 35-year-old woman. Arch Pathol Lab Med 2006; 130:113-114.
12. Deavers MT, Malpica A, Ordonez NG, Suva EG. Ovarian steroid cell tumors: an immunohistochemical study including a comparison of calretinin with inhibin. Int J Gynecol Pathol 2003;22:162-167.
13. Wang PH, Chao HT, Lee WL. Use of a long-acting gonadotropin- releasing hormone agonist for treatment of steroid cell tumors of the ovary. Fertil Steril 1998;69:353-355.
HORNG-JYH TSAI1, SHU-CHEN CHEN2,3, HSIAO-YUN WEI1, & GIN-DEN CHEN1
1 Department of Obstetrics and Gynecology, Chung-Shan Medical University and Hospital, Taichung, Taiwan, 2 School of
Nursing, Chung-Shan Medical University, Taichung, Taiwan, and 3School of Nursing, Central Taichung Science and
Technology University, Taichung, Taiwan
(Received 21 September 2006; revised 2 November 2006; accepted 21 November 2006)
Correspondence: H.-J. Tsai, Department of Obstetrics and Gynecology, Chung-Shan Medical University and Hospital, 110 section 1, Chien-Kuo North Road, Taichung, Taiwan 402. Tel: 886 4 2473 9595. Fax: 886 4 2473 8493. E-mail: cshy076@csh.org.tw
Copyright Taylor & Francis Ltd. Feb 2007
(c) 2007 Gynecological Endocrinology. Provided by ProQuest Information and Learning. All rights Reserved.