The effect of D-Ala2, MePhe4, Met-(0)enkephalinol (Sandoz
FK 33-824; 0.5 mg, im) on pituitary
hormone secretion was studied in 11 patients with
Addison's disease and 11 patients with
ACTH-dependent
Cushing's disease. In patients with
Addison's disease, a pronounced fall of plasma
ACTH levels was observed (P less than 0.005). The
ACTH response to
FK 33--824 was partially reversed by
naloxone (4 mg, iv). In patients with
Cushing's disease, no unequivocal decrease in either
ACTH or
cortisol was seen. Moreover,
FK 33--824 failed to influence the
vasopressin-induced
ACTH increase in 5 patients with
Cushing's disease. In patients with
cortisol deficiency due to either
Addison's disease or bilateral
adrenalectomy for
Cushing's disease,
FK 33--824 led to increases in PRL and GH similar to those described in normal subjects. However, in the presence of longstanding
hypercortisolism, the PRL increase was significantly diminished, and the GH response to
FK 33--824 was completely abolished. Our results suggest that in
Addison's disease ACTH release is influenced by inhibitory
opiate receptors. In patients with
Cushing's disease,
ACTH secretion is insensitive to FK 33-284, presumably because of an autonomous
pituitary adenoma or hypothalamic derangement. The impairment of the PRL and GH responses to
FK 33--824 in
Cushing's syndrome seems to reflect a direct action of the elevated
cortisol level, for it is not seen after bilateral
adrenalectomy.