Abstract
A sensitive radioimmunoassay for ACTH was established on the basis of discovery of an increase in binding of 125I-ACTH in proportion to an increase in unlabelled ACTH when a small amount of 125I-ACTH was added to antisera of a relatively high concentration (Matsukura et al.). Talc was used to separate free from bound 125I-ACTH. The minimal detectable value was 1 to 2 pg. By using this assay procedure, plasma ACTH levels were measured in normal subjects and patients with pituitaryadrenal dysfunction.
In normal subjects, plasma ACTH levels were high in the morning and low in the evening, showing a marked diurnal rhythm. Insulin-induced hypoglycemia or administration of pyrogen significantly raised plasma ACTH levels in all the normal subjects tested. Intravenous infusion of 5 g of metyrapone caused a significant rise in plasma ACTH levels. These results support the hypothesis that ACTH secretion in normal subjects is regulated by 3 factors, namely circadian rhythm, stress and negative feedback mechanism. Plasma ACTH levels also rose significantly following intravenous administration of 1 mg of glucagon with the mean peak levels of 284.5 ± 81.1 pg/ml in normal subjects. They increased slightly upon administration of 1 mg of synthetic 1-24 ACTH (tetracosactide), but not upon that of 10 U of oxytocin. The mechanism by which certain peptides stimulate secretion ofACTH remains unsolved.
In patients with Addison's disease, plasma ACTH levels were extremely elevated in the morning, although the circadian rhythm was maintained. Intravenous infusion of 100 mg of corticosterone or cortisol significantly lowered plasma ACTH levels in all the Addisonian patients tested. Cortisol was more effective than corticosterone in suppressing ACTH secretion.
In patients with untreated Cushing's syndrome due to adrenal hyperplasia, basal morning plasma ACTH levels were only moderately elevated, although normal diurnal rhythm was lacking. On the contrary, plasma ACTH were undetectable in patients with Cushing's syndrome due to adrenal adenoma. Plasma ACTH responses to insulin-induced hypoglycemia and to administration of glucagon or synthetic ACTH were either significantly blunted or absent in patients with Cushing's syndrome due to adrenal hyperplasia. However, plasma ACTH responded significantly to administration of lysine-8-vasopressin.
Patients with hypopituitarism had low basal plasma ACTH levels and showed no response of plasma ACTH to a single oral administration of metyrapone (30 mg/kg) at midnight, whereas normal subjects showed a remarkable increase in plasma ACTH.
Assay of plasma ACTH may prove to be of value in differentiating primary adrenocortical insufficiency from the secondary one and especially in helping to evaluate etiology of Cushing's syndrome.
