ascorbic-acid and Cushing-Syndrome

Topics: Ascorbic Acid; Avitaminosis; Blood Vessels; Cushing Syndrome; Diagnosis, Differential; Ehlers-Danlos Syndrome; Hemophilia A; Hemorrhagic Disorders; Humans; Purpura; Telangiectasia, Hereditary Hemorrhagic; Thrombocytopenia; Vascular Diseases

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.

Topics: Adolescent; Adrenal Cortex Diseases; Adrenocorticotropic Hormone; Adult; Ascorbic Acid; Biological Assay; Child; Cosyntropin; Cushing Syndrome; Dexamethasone; Female; Histocytochemistry; Humans; Hydrocortisone; Immunoglobulin G; Peptide Fragments

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Ascorbic Acid; Blood Chemical Analysis; Chromatography; Cushing Syndrome; Humans; Hydrocortisone; Hypophysectomy; Rats; Research