Impact of clinical, hormonal, radiological, and immunohistochemical studies on the diagnosis of postmenopausal hyperandrogenism

Abstract

Objective: Evaluation of postmenopausal women with suspicion of androgen-secreting tumor. Design and patients: We retrospectively studied 22 postmenopausal women referred to our center for suspicion of androgen-secreting tumor. All patients had clinical, biological, and morphological evaluation. In absence of adrenal tumors, ovarian surgery was most often proposed and immunohistochemistry (IHC) studies were performed. Results: Ovarian tumors were detected by ultrasound and/or magnetic resonance imaging in eight patients. Two adrenal androgen-secreting tumors were diagnosed by an adrenal computed tomography (CT) scan. The clinical presentation of the women with or without tumors was similar. Nevertheless, women with tumor exhibited significantly higher testosterone levels and lower basal FSH and LH levels than the other women (2.6G2.7 vs 0.9G0.9 ng/ml, P!0.05; 26.5G22.9 vs 66.5G 26.0 IU/l, P!0.01; and 12.0G8.6 vs 24.1G8.9 IU/l, P!0.05 respectively). Based on a likelihood ratio test, patients with a tumor had 8.4 and 10.8 times higher risk of having a testosterone level R1.4 ng/ml or an FSH level %35 IU/l. Finally, IHC analysis with an anti-P450c17a antibody allowed the identification of an elevated number of ovarian androgen-producing cells in five patients in whom no tumor was found. Conclusions: Androgen-secreting tumors are clinically difficult to discriminate from other causes of postmenopausal hyperandrogenism. Testosterone and FSH were the two discriminative markers in a multivariate analysis. Ovarian and adrenal tumors were detected by imaging studies. However, ovarian non-tumoral causes of hyperandrogenism may be difficult to detect with conventional histology.

MANAGEMENT OF ENDOCRINE DISEASE: Hyperandrogenism after menopause

“…1). However, there is a wide variation in testosterone cut-offs employed between the different studies mainly due to the relative paucity of data in postmenopausal women (12,16,17,18).…”

“…Androgen-secreting neoplasms are usually associated with absolute hyperandrogenism (testosterone levels O100-140 ng/dl); this relatively broad range of testosterone cut-offs reflects the wide variation of testosterone levels in the different studies and the lack of meticulous registration of such patients (7,8,12,17,18). The androgen-secreting neoplasms usually have distinct clinical features and have traditionally been associated with a rapid onset of signs and symptoms resulting in various degrees of virilization (7,8).…”

“…2.5 cm) and other signs of virilization should always direct toward OH or an androgen secreting neoplasm even if symptom progression is not rapid (73). However, the clinical phenotype alone cannot reliably discriminate tumorous from nontumorous causes of hyperandrogenism (12). Conversely, a florid clinical phenotype may be suggestive of an underlying endocrinopathy such as CS or acromegaly, although mild cases may be diagnosed with substantial delay (48,50).…”

“…The ovarian tumors are usually large and can be identified with transvaginal ultrasonography and/or magnetic resonance imaging (MRI). It has been suggested that MRI may be more sensitive and specific than ultrasonography in the identification of ovarian tumors, as it has shown the highest positive and negative predictive value (78 and 100% respectively) in the largest and most detailed study evaluating postmenopausal women with and without tumorous hyperandrogenism (12). Occasionally, some tumors may be of relatively small size and elude radiological detection (18).…”

“…However, the extent of laboratory investigation, the imaging modalities required, and the androgen cut-off levels that need to be employed for differential diagnosis are not clearly defined. In fact, there is a paucity of studies addressing these issues in postmenopausal hyperandrogenic women (7,8,12). …”