Released on 2012-05-11
Take home messages:
1. Virilization of rapid onset should always raise suspicion of an androgen secreting tumor.
2. Levels of both DEHAS and Testosterone are usually elevated in androgen secreting adrenal tumors - whereas isolated elevation of Testosterone is more common in ovarian tumors.
3. Androgen secreting adrenal tumors tend to be large enough to show up in imaging studies, whereas ovarian tumors are often small and undetectable or easily missed.
4. Even with prompt treatment, the signs of virilization take months to regress.
Androgen secreting ovarian tumors are rare, accounting for less than 0.1% of all tumors of the ovary. Of these, SLCT (which arise from sex cord stromal cells), are the commonest type.
The majority of SLCT occur in women of reproductive age, although premenarcheal and postmenopausal females can be affected as well.
SLCT are usually unilateral, small and benign, with a low potential for malignant transformation.
The remainder of this discussion talks about SLCT, although most of the facts are applicable to other androgen-secreting ovarian tumors.
The classical clinical features are due to the androgen excess, and include menstrual irregularities, hirsutism, deepening of voice, clitoromegaly, increased muscle mass and loss of the normal female body contour. These symptoms and signs typically progress rapidly.
Note that the sensitivity of the body to testosterone varies from person to person - thus similar elevations may have widely varying effects in different individuals.
A full hormonal profile should be performed in these patients. Features suggestive of SLCT include an isolated increase in testosterone levels, but normal 17-hydroxyprogesterone, DHEAS and cortisol.
If the hormonal profile is equivocal, a 48 hour dexamethasone suppression test can be performed. If DHEAS and cortisol levels are suppressed but testosterone levels are unaffected, this is supportive of an androgen secreting ovarian tumor.
Even when the diagnosis is suspected, confirmation via imaging is often tricky. These tumors are often very small, and may not be detectable via ultrasound or CT scans.
If imaging studies are inconclusive, but clinical and biochemical studies suggest the diagnosis, sampling of the ovarian veins for testosterone levels may be considered, with a high testosterone concentration establishing the diagnosis. Note that this test is complex, with a high risk of hemorrhage - it should only be performed at a unit with the relevant expertise.
Salpingo-oophorectomy of the affected side is usually adequate in young patients (in postmenopausal patients a total abdominal hysterectomy + bilateral salpingo-oophorectomy may be considered instead).
Histopathological examination and immunohistochemistry should be performed on the specimen, to establish the histologic subtype. This information will also be useful in determining the prognosis.
Postoperatively, assays show a rapid decline in serum testosterone levels - but note that it may take many months for the signs of virilization to regress.
Around 33% of patients experience a relapse following surgery. This is more common with poorly differentiated tumors.
Note that some tumors are gonadotrophin dependent - thus, certain patients may benefit from adjuvant therapy with GnRH analogs. In addition, adjuvant chemotherapy may be considered in patients with poorly differentiated tumors.
AFP: evaluation and treatment of women with hirsutism (June 2003)
Lancet: Hirsutism (January 1997)
Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline (february 2008)
European journal of endocrinology: investigation of patients with atypical or severe hyperandrogenaemia including androgen-secreting ovarian teratoma (2010)
Clinical Endocrinology: selective venous sampling for androgen producing ovarian pathology (april 2009)
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