NYCTOHEMERAL VARIATION AND SUPPRESSIBILITY OF PLASMA ACTH IN VARIOUS STAGES OF CUSHINGS-DISEASE

In order to define nyctohemeral plasma ACTH secretory patterns, frequent plasma ACTH samples were obtained in 7 patients with untreated Cushing''s disease (i.e., pituitary-dependent Cushing''s syndrome), 5 Cushing''s patients treated by bilateral adrenalectomy, 4 of whom had Nelson''s syndrome and 1 patient with 21-hydroxylase deficiency (congenital adrenal hyperplasia). A nyctohemeral rhythm of plasma ACTH concentration was apparent in the 1 patient with the adrenogenital syndrome but not in those with Nelson''s syndrome or Cushing''s disease. The effect of graded doses of dexamethasone, 2, 8 or 32 mg/24 h period, on plasma ACTH concentrations was studied in patients with untreated or treated Cushing''s disease or Nelson''s syndrome. In all of these hypercorticotrophic states, the mean plasma ACTH concentration was not significantly affected by the smallest dose of dexamethasone, was partially suppressed by the intermediate dose and further suppressed by the largest dose. The patient with congenital adrenal hyperplasia and elevated plasma ACTH concentrations showed complete suppression of plasma ACTH levels following the smallest dose of dexamethasone. There is probably resistance to ACTH suppression by dexamethasone in all stages of Cushing''s disease, and negative feedback of glucocorticoids may be involved in the pathogenesis of this disease.