Unusual Virilization in Girls with Juvenile Granulosa Cell Tumors of the Ovary Is Related to Intratumoral Aromatase Deficiency

Kalfa, Nicolas; Meduri, Géri; Philibert, Pascal; Patte, Catherine; Boizet-Bonhoure, Brigitte; Thibaut, E; Pienkowski, Catherine; Jaubert, Françis; Misrahi, Micheline; Sultan, Charles

doi:10.1159/000313396

Cited by 19 publications

(19 citation statements)

References 64 publications

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“…The ovarian tumors of six of our T patients are known to secrete androgens, although this occurs infrequently in granulosa cell tumors (42). Two ovarian tumors found in our cohort, a gastrointestinal tumor with bilateral ovarian metastases and a serous cystadenoma, were not known to be steroidogenic.…”

Section: Discussionmentioning

confidence: 69%

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

Sarfati

Bachelot

Coussieu

et al. 2011

European Journal of Endocrinology

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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.

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Section: Discussionmentioning

confidence: 69%

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

Sarfati

Bachelot

Coussieu

et al. 2011

European Journal of Endocrinology

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“…The most frequent presentation in prepubertal girls is precocity. [34] Clinical manifestations may also include hyperandrogenism, pleural effusion, ascites, or surgical emergency rarely as in our case.…”

Section: Discussionmentioning

confidence: 79%

Juvenile granulosa cell tumor presenting as isosexual precocious puberty: A case report and review of literature

Haroon

Agarwal

Pandey

et al. 2013

Indian J Endocr Metab

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The differential diagnosis for precocious puberty in a young female includes peripheral causes. This case report documents a rare cause of isosexual precocious puberty, a juvenile granulosa cell tumor of the ovary–and a brief literature review. A 7-year-old girl presented with rapid onset of pubertal development and elevated estradiol levels. Abdominal ultrasound revealed a mass in the right adnexa. Other causes of precocious puberty were excluded. Elective surgery was planned, but the patient presented to the emergency room with torsion of ovary. She underwent an exploratory laparotomy for tumor resection and right salpingo oophorectomy. Pathology reported a juvenile granulosa cell tumor of the ovary. Postoperatively, she experienced a cessation of vaginal bleeding and estradiol levels normalized. Early stage disease has good prognosis. Adjuvant chemotherapy is not indicated in this setting.

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“…In line with the present findings, previous reports have shown that healthy tissues, in which aromatase expression is present, lose this expression when they become neoplastic. Kalfa et al . described 30 cases of juvenile granulosa cell tumor of the ovary and showed absence of aromatase expression in all patients with concurrent hyperandrogenism (6 cases), although the enzyme is normally expressed in healthy granulosa cells and despite the fact that its presence has been described in granulosa cell tumors .…”

Section: Discussionmentioning

confidence: 99%

Aromatase P450 expression in human pituitary adenomas

et al. 2014

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Estrogen has been shown to play an important role in pituitary tumor pathogenesis. In humans, this biosynthesis is mediated by aromatase, an enzyme that converts androgens to estrogens. Just a few studies about aromatase expression in human pituitary gland, both in normal and pathological ones, are found in the literature. This study aimed to assess aromatase enzyme expression in human pituitary adenomas and associate it with gender, tumor size and tumor subtype. We conducted a cross-sectional study, reviewed clinical data and surgical specimens of consecutive 65 patients (35 women and 30 men) with anatomopathologic diagnosis of pituitary adenoma who underwent adenomectomy at a neurosurgical referral center in southern Brazil. Immunohistochemistry was performed to assess aromatase expression and define tumor subtype, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to estimate aromatase gene expression. Mean patient age was 45.6 (±13.3) years (range, 18 to 73 years), 86.2% of our samples were macroadenomas while 13.8% were classified as microadenomas. Based on clinical and immunohistochemical data, 23 (35.4%) patients had non-functioning adenomas, 19 (29.2%) had somatotroph adenomas (acromegaly), 12 (18.5%) had lactotroph adenomas (hyperprolactinemic syndrome), and 11 (16.9%) had corticotroph adenomas (Cushing's disease). Immunohistochemical analysis was performed in 59 cases, and 58 (98.3%) showed no aromatase expression. Quantification by qRT-PCR was performed in 43 samples, and 36 (83.7%) revealed no gene expression. Among tumor specimens examined by both techniques (37 cases), 30 showed no gene or protein expression (concordance index, 0.81). It is possible to mention that aromatase expression was lost in most pituitary adenomas, regardless of gender, tumor subtype, or tumor size.

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Unusual Virilization in Girls with Juvenile Granulosa Cell Tumors of the Ovary Is Related to Intratumoral Aromatase Deficiency

Cited by 19 publications

References 64 publications

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

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

Juvenile granulosa cell tumor presenting as isosexual precocious puberty: A case report and review of literature

Aromatase P450 expression in human pituitary adenomas

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