Investigation of patients with atypical or severe hyperandrogenaemia including androgen-secreting ovarian teratoma

Dennedy, Michael Conall; Smith, Diarmuid; O’Shea, Donal; McKenna, T. J.

doi:10.1530/eje-09-0576

Cited by 27 publications

(15 citation statements)

References 43 publications

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“…It is known that high androgen concentrations may disturb the development of (pre)antral follicles, both if hyperandrogenism occurs prenatally (Wu et al. , 2010) or postnatally (Dennedy et al. , 2010).…”

Section: Discussionmentioning

confidence: 99%

Early breast development in girls after prenatal exposure to non‐persistent pesticides

et al. 2012

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Contemporary American and European girls experience breast development at earlier ages compared with 15-20 years ago. Alterations in BMI alone cannot account for these changes. Several currently used pesticides possess endocrine disrupting properties and may interfere with reproductive development, but human data are sparse. We examined girls whose mothers worked in greenhouses in the first trimester of pregnancy to assess the long-term effects of prenatal pesticide exposure on puberty. Mothers were prenatally categorized as exposed or unexposed to pesticides. We studied the offspring of these greenhouse workers, and evaluated the anthropometry, pubertal staging in the girls, and blood samples were drawn at 3 months of age (n = 90) and again once at school age (6-11 years, n = 83). No clinical and biochemical differences were found between the exposed and unexposed girls at 3 months of age. Mean onset of B2+ was 8.9 years (95% CI: 8.2; 9.7) in prenatally exposed girls, compared with 10.4 years (9.2; 17.6) in the unexposed (p = 0.05), and 10.0 (9.7-10.3) years in a Danish reference population (p = 0.001). Exposed girls had higher serum androstenedione levels (geometric means: 0.58 vs. 0.79 nmol/L, p = 0.046) and lower Anti-Müllerian Hormone (AMH) compared with the unexposed (geometric means: 16.4 vs. 21.3 pmol/L, p > 0.05) and the reference group (20.2 pmol/L, p = 0.012). Levels of testosterone, estradiol, prolactin, FSH, LH, SHBG, DHEAS, DHT, Inhibin A and Inhibin B did not differ between the groups. In conclusion, our findings suggest that prenatal exposure to currently approved pesticides may cause earlier breast development in girls. This association appeared not to be because of changes in gonadotropins, but rather to higher androgen levels, which indirectly may increase oestrogens through aromatization. In addition, lower serum AMH levels indicated a reduced pool of antral ovarian follicles. The long-term consequences of our findings with regard to establishment of future reproductive function still remain unknown.

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Section: Discussionmentioning

confidence: 99%

Early breast development in girls after prenatal exposure to non‐persistent pesticides

et al. 2012

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“…They are commonly associated with high testosterone levels (7, 8) . High plasma levels of testosterone associated with normal dehydroepiandrosterone sulfate (DHEAS) concentration are indicative of ovarian hyperthecosis or androgen-secreting ovarian tumors such as Leydig–Sertoli tumors (9, 10, 11) . In contrast, high levels of DHEAS are indicative of adrenocortical adenoma of zona reticularis (ZR).…”

Section: Introductionmentioning

confidence: 99%

Steroidogenic enzyme profile in an androgen-secreting adrenocortical oncocytoma associated with hirsustism

Nomigni¹,

Ouzounian²,

Benoit³

et al. 2015

Endocrine Connections

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Hirsutism induced by hyperandrogenism can be associated with polycystic ovary syndrome, 21-hydroxylase (OH) deficiency or androgen-secreting tumors, including ovarian and adrenal tumors. Adrenal androgen-secreting tumors are frequently malignant. Adrenal oncocytomas represent rare causes of hyperandrogenism. The aim of the study was to investigate steroidogenic enzyme expression and steroid secretion in an androgen-secreting adrenal oncocytoma in a young woman presenting with hirsutism. Hyperandrogenism was diagnosed on the basis of elevated plasma Δ4-androstenedione and testosterone levels. Pelvic ultrasound was normal, CT scanning revealed a right adrenal mass. Androgens were assessed in adrenal and ovarian vein samples and proved a right adrenal origin. Adrenalectomy normalized androgen levels and the adrenal tumor was diagnosed as an oncocytoma. Real time-PCR, immunohistochemistry and cell culture studies were performed on tumor explants to investigate the steroid secretion profile. Among enzymes required for cortisol synthesis, 17α-OH and 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) were highly expressed whereas 21-OH and 11β-OH were weakly produced at the mRNA and/or protein levels. Enzymes involved in testosterone production, 17β-HSD5 and 17β-HSD3, were also detected. ACTH receptor was present in the tissue. Cortisol, Δ4-androstenedione and testosterone secretions by cultured cells were increased by ACTH. These results provide the first demonstration, to our knowledge, of abnormal expression profile of steroidogenic enzymes in an adrenocortical oncocytoma. Our results also indicate that Δ4-androstenedione hypersecretion resulted from high 17α-OH and 3β-HSD2 expression in combination with low expression of 21-OH and 11β-OH. Testosterone production was ascribed to occurrence of 17β-HSD5 and 17β-HSD3. Finally, our results indicate that androgen secretion was stimulated by ACTH.

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“…Clitoromegaly (clitoral size O1.5! 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).…”

Section: Diagnosis and Differential Diagnosismentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Hyperandrogenism after menopause

Markopoulos

Kassi

Alexandraki

et al. 2015

European Journal of Endocrinology

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Postmenopausal hyperandrogenism is a state of relative or absolute androgen excess originating from either the adrenals and/or the ovaries, clinically manifested as the appearance and/or increase in terminal hair growth or the development of symptoms/signs of virilization. In either settings, physicians need to evaluate such patients and exclude the presence of the relatively rare but potentially life-threatening underlying tumorous causes, particularly adrenal androgen-secreting tumors. It has been suggested that the rapidity of onset along with severity of symptom and the degree of androgen excess followed by relevant imaging studies may suffice to identify the source of excessive androgen secretion. However, up to date, there is no consensus regarding specific clinical and hormonal indices and/or imaging modalities required for diagnostic certainty. This is particularly relevant as the aging population is increasing and more cases of postmenopausal women with clinical/biochemical evidence of hyperandrogenism may become apparent. Furthermore, the long-term sequels of nontumorous hyperandrogenism in postmenopausal women in respect to cardiovascular morbidity and mortality still remain unsettled. This review delineates the etiology and pathophysiology of relative and absolute androgen excess in postmenopausal women. Also, it attempts to unravel distinctive clinical features along with specific hormonal cut-off levels and/or appropriate imaging modalities for the facilitation of the differential diagnosis and the identification of potential long-term sequels.

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Investigation of patients with atypical or severe hyperandrogenaemia including androgen-secreting ovarian teratoma

Cited by 27 publications

References 43 publications

Early breast development in girls after prenatal exposure to non‐persistent pesticides

Early breast development in girls after prenatal exposure to non‐persistent pesticides

Steroidogenic enzyme profile in an androgen-secreting adrenocortical oncocytoma associated with hirsustism

MANAGEMENT OF ENDOCRINE DISEASE: Hyperandrogenism after menopause

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