title: Immunoglobulins of patients with Cushing's syndrome due to pigmented adrenocortical micronodular dysplasia stimulate in vitro steroidogenesis.
abstract: The putative stimulation of adrenal steroid production by immunoglobulins (Igs) of five patients with pigmented adrenocortical micronodular dysplasia and clinical Cushing's syndrome was investigated. Ascorbate depletion, a process linked to steroid production, was measured by a cyto-chemical bioassay employing guinea pig adrenal explants in organ culture and exposed to IgG from the patients and normal subjects. We also measured cortisol production by these segments during a 5-h culture period using a RIA. For positive reference values we studied the effects of ACTH-(1-39), ACTH-(1-24), ACTH-(11-24), and ACTH-(18-39) on in vitro ascorbate depletion and cortisol production. Both ACTH-(1-39) and ACTH-(1-24) depleted ascorbate and stimulated cortisol production in adrenal cells. The dose-response kinetics of the peptides were bell-shaped; maximal responses were reached in both instances at 1 fmol/L to 10 pmol/L. In all tests, stimulation of in vitro cortisol production was paralleled by ascorbate depletion. ACTH-(18-39) also stimulated ascorbate depletion and cortisol production, but at one concentration only (100 fmol/L), and TSH and LH had no effect. Protein-A-Sepharose-purified IgG preparations of the five patients stimulated ascorbate depletion and/or cortisol production in a dose-dependent fashion; however, the responses occurred over a narrow concentration range (15-150 micrograms IgG/mL culture fluid). These observations support the hypothesis that the hypercortisolism of the syndrome of pigmented adrenocortical micronodular dysplasia is due to circulating Igs that stimulate adrenal steroidogenesis.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: N M
authors.initials: NM
authors.lastname: Wulffraat
authors.forename: H A
authors.initials: HA
authors.lastname: Drexhage
authors.forename: W M
authors.initials: WM
authors.lastname: Wiersinga
authors.forename: R D
authors.initials: RD
authors.lastname: van der Gaag
authors.forename: P
authors.initials: P
authors.lastname: Jeucken
authors.forename: J A
authors.initials: JA
authors.lastname: Mol
mesh_terms: D000293:Adolescent; D000303:Adrenal Cortex Diseases / Q000150:complications* / Q000276:immunology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001205:Ascorbic Acid / Q000378:metabolism; D001681:Biological Assay; D002648:Child; D003366:Cosyntropin / Q000494:pharmacology; D003480:Cushing Syndrome / Q000209:etiology / Q000276:immunology*; D003907:Dexamethasone; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis; D010446:Peptide Fragments / Q000494:pharmacology
chemical_list: D007074:Immunoglobulin G; D010446:Peptide Fragments; D003366:Cosyntropin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D001205:Ascorbic Acid; D006854:Hydrocortisone