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.