title: Analysis of cortisol secretion in hormonally inactive adrenocortical incidentalomas: study of in vitro steroid secretion and immunohistochemical localization of steroidogenic enzymes.
abstract: Adrenal incidentalomas have recently increased in incidence, and thus it has become important to establish clinical management of these patients. It is also important to evaluate whether these tumors are different from preclinical or overt Cushing's syndrome in their steroidogenesis. In this study, we therefore examined steroidogenesis of hormonally inactive adrenal incidentalomas via short-term culture of tumor specimens, in addition to an immunohistochemical study of steroidogenic enzymes. Five patients (two men and three women) diagnosed with adrenocortical incidentaloma without any clinical signs of adrenocortical hormonal excess except for hypertension and disturbed glucose tolerance, were recruited for this study. Hormonal findings, including circadian rhythms for cortisol and ACTH secretion, the response of ACTH to CRH infusion and results of dexamethasone suppression test were all within normal limits in these patients. Immunoreactivity for all steroidogenic enzymes involved in cortisol production was detected in tumor cells in all cases examined. Results of in vitro steroidogenesis analysis using short-term culture revealed that levels of cortisol secretion varied among the cases. There were no differences in the immunolocalization of steroidogenic enzymes and/or the levels of cortisol secretion between these hormonally inactive tumors and preclinical and/or overt Cushing's syndrome. Dehydroepiandrosterone-sulfotransferase (DHEA-ST) immunoreactivity in nonneoplastic regions was suppressed in one case in which the tumor secreted cortisol similar to preclinical and/or overt Cushing's syndrome. These results demonstrate that the levels of in vitro steroid production and/or the immunolocalization of steroidogenic enzymes in hormonally inactive adrenocortical tumors vary markedly and are not overtly different from those of preclinical and/or overt Cushing's syndrome.
authors.affiliation: Third Department of Internal Medicine, Fukushima Medical University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Midorikawa
authors.forename: H
authors.initials: H
authors.lastname: Sanada
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Sasano
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis; D000236:Adenoma / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000032:analysis; D002940:Circadian Rhythm; D003346:Corticotropin-Releasing Hormone; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003907:Dexamethasone; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011374:Progesterone / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000032:analysis; D013255:Steroid 21-Hydroxylase / Q000032:analysis; D015238:Sulfotransferases / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: D011374:Progesterone; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase; D006854:Hydrocortisone