Virilizing ovarian steroid cell tumor in a 40 year old South Indian female: a case report
Virilism is the masculinization and enhancement of male secondary sexual characteristics in females. The etiology is usually of adrenal or ovarian origin. Here we report a case of virilizing Leydig cell type, steroid cell tumor of the left ovary, in a 40 year old female who presented with clinical signs and symptoms of virilization: deepening of voice, hirsutism (Ferriman-Gallwey score 26), clitoromegaly, and androgenic alopecia. On further evaluation, laboratory investigations revealed hyperandrogenism in the male range. Basal testosterone values were elevated. Folicle Stimulating Hormone and Luteinising Hormone levels were within normal limits. Dexamethasone suppression test did not alter cortisol or testosterone levels. An ovarian mass was confirmed radiologically. Following a total abdominal hysterectomy with bilateral salpingoophorectomy, histopathological studies confirmed a left sided steroid-cell ovarian tumor, Leydig cell type (stage T1N0M0), which proved to the etiology of virilization in this patient. Post-operatively her serum testosterone levels declined with near-complete reversal of symptoms over time.
KeywordsLeydig Cell Dexamethasone Suppression Test Leydig Cell Tumor Steroid Cell Tumor Androgenic Alopecia
List of abbreviations
Follicle stimulating hormone
Magnetic resonance imaging
Thyroid stimulating hormone.
Hirsutism is defined as excessive male-pattern hair growth. Virilization refers to a condition in which the androgen levels are sufficiently high to cause additional signs and symptoms such as deepening of the voice, breast atrophy, increased muscle bulk, clitoromegaly, and increased libido . Virilizing ovarian tumors account for 0.1% of all ovarian tumors . Here we report a 40-year-old woman who presented to the gynecology outpatient department with signs and symptoms of virilization. After investigations and histopathological examination, the patient was found to have a steroid-cell ovarian tumor, Leydig-cell type, which proved to the etiology of virilization in this patient.
A 40-year-old multiparous woman from South India was referred to our Gynecology department with a two year history of progressive deepening of voice, an increase in facial and body hair, and frontal balding; her symptoms have worsened over the past six months. She attained menarche at the age of 14 years, and has had irregular menses lasting 3 to 4 days, every three or four months since then. She is a mother of two healthy boys, aged 12 and 15 years, both of whom were delivered vaginally without complications. The patient has been amenorrheic for the past four and a half years. There is no history suggestive of hypothyroidism or hyperprolactinemia. There is no significant family history, other than the fact that her mother attained menopause at the age of 40 years. She is a known hypertensive on treatment with calcium channel blockers. She is not on any other medications.
Random blood sugar
< 1.0 mcg/dl
17 - hydroxyprogesterone
Pre-operative 2300 ng/dl
Post-operative 72 ng/dl
Free Testosterone (pre-operative)
Virilizing ovarian tumors account for less than 5% of all ovarian neoplasms . Sex cord-stromal tumors, are derived from the sex cord and stromal components of the developing gonad . Steroid cell tumors are a subtype of ovarian sex cord-stromal tumors that are composed entirely of steroid-secreting cells and account for 0.1% of all ovarian neoplasms . Steroid cell tumors are usually virilizing, frequently secreting testosterone; however, they may be endocrinologically inert or estrogenic. As many as one-quarter of steroid tumors exhibit malignant behavior .
Steroid cell tumors are further subclassified into stromal luteoma, Leydig cell tumors (hilar and nonhilar), and steroid cell tumors that are not otherwise specific . Most pure Leydig cell tumors of the ovary arise from the hilus cells, or hilar-Leydig cells, which have the morphologic features of testicular Leydig cells and can be found in the ovarian hilus in more than 80% of adult women. These tumors are classified under the category of steroid cell tumors (lipid cell tumors) because they may be difficult or impossible to differentiate histologically from ovarian tumors of other steroid cell types .
The clinical manifestations are to a large extent determined by the age of presentation, hormonal activity, and virilizing properties of the tumor. Virilization or hirsutism is encountered with three fourths of Leydig cell tumors .
The clinical presentation may take many forms, including abdominal pain, abdominal distention, and bloating. However, the more noticeable presentations are those associated with the hormonal activity and virilizing properties of the tumor . Signs and symptoms of masculinizing tumors usually take place in two definite phases, an early phase of defeminization and a subsequent phase of masculinization. Typically, a menstruating female will first notice oligomenorrhea or amenorrhea. There is regression of the breasts and external genitalia, atrophy of the uterus and adnexa, and loss of the female body contour. This is followed by hirsutism, acne, clitoral enlargement, increased libido, sterility, enlargement of the larynx, deepening of the voice, and temporal alopecia [9, 10]. On the other hand, these tumors may produce little or no androgenic activity and could, in fact, show some evidence of estrogenic effect [4, 10].
With regard to blood investigations, detecting the source of the androgenic tumor is a process of exclusion. In our patient, the high serum free and total testosterone confirmed the presence of a virilizing neoplasm. A dexamethasone suppression test failed to alter basal values, moreover, 17-hydroxyprogesterone levels were also within normal limits; this ruled out a potential adrenal source of the androgens [11, 12].
On radiological imaging, appearances of virilizing tumors of the ovary depend, to some extent, on the tumor type. Virilizing steroid cell tumors of the ovary are usually one sided and often very small, measuring only slightly bigger than the normal ovary [9, 10]. They are usually confined to the ovary at presentation, predominantly solid or mostly solid, non-calcified, and not associated with ascites. Small steroid cell tumors have been described as slightly hypoechoic or hyperechoic (compared to the ovary) with high diastolic flow on Doppler interrogation. They may be difficult to identify on radiological imaging, in part because they are isoechoic to the uterus on ultrasound and isoattenuating on CT [13, 14]. Techniques such as MRI with phased array coils, or color Doppler imaging, can possibly detect smaller tumors than more conventional imaging methods [13, 14, 15]. In our patient, abdominal ultrasound examination was unremarkable except for the presence of ovarian cysts. A CT-scan and an MRI helped in confirming the existence of a mass lesion involving the left adnexa. It was the post-operative histopathological study, however, that helped in clinching the final diagnosis as the presence of Reinke's crystalloid is diagnostic for Leydig cell tumors [4, 5, 9].
Though steroid cell tumors of Leydig-cell subtype are usually benign, there is still a potential risk for malignant transformation [5, 9, 10]. Surgery remains the mainstay in the management of these neoplasms as, in addition to overcoming the above risk, however small, the removal of the tumor is usually followed by near-complete regression of the presenting symptoms. Initially, the signs of defeminization, such as flattened breasts and loss of fat around the hips, are reversed. Subsequent to this, the virilizing effects disappear slowly; the hypertrophied clitoris and the deepening of the voice, however, frequently persist [6, 10].
A patient who presents with virilism should be investigated systematically to determine if the high testosterone levels are of an adrenal or ovarian origin. In this patient, hematological investigations ruled out an adrenal cause. Radiological imaging proved to find that the cause of virilization was of an ovarian etiology. Surgical intervention was sought and the diagnosis of virilizing ovarian tumor was made by histopathologic examination.
It was a harrowing experience for me when I started balding and growing excessive hair all over my body. My fears increased as my friends and relatives started noticing a change in my voice. When the doctors told me I had a tumor, I felt my outcome was bleak. After the operation, my physical appearance improved, and my social life has returned to normal. I am grateful to the doctors for all they have done.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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