POTENTIATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSE TO METYRAPONE BY l-DOPA IN ACROMEGALIC PATIENTS

The effects of l -DOPA administration on hypothalamic-pituitary-adrenal function were studied in five normal subjects and in five patients with active acromegaly. In acromegalic patients, oral l -DOPA (500 mg every 4 h for six doses) failed to alter the urinary excretion of 17-hydroxycorticoids (17-OHCS), 17-oxosteroids (17-OS), and tetrahydro-11-desoxycortisol (tetrahydro-comp S). However, when cortisol synthesis was blocked with oral metyrapone, enhancement of excretion of 17-OHCS, 17-OS, and tetrahydro-comp S by l -DOPA became apparent in acromegalic patients but not in the normals. In patients with acromegaly, on the day of metyrapone administration, the mean excretion rates of 17-OHCS, 17-OS, and of tetrahydro-comp S were 8.6 mg, 6.4 mg and 4.1 mg/24 h, respectively. When 500 mg l -DOPA was co-administered with metyrapone, the corresponding values increased significantly (P<0.01) to 14.9 mg, 9.0 mg and 7.7 mg/24 h. This effect of l -DOPA was not observed in the normal subjects. It was concluded that l -DOPA markedly enhanced the hypothalamic-pituitary-adrenal response to metyrapone in acromegalic patients, but not in normal subjects. l -DOPA (or one of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of ACTH. The unusual pituitary-adrenal response to l -DOPA in acromegaly may reflect: (1) a supersensitive reaction of the pituitary-adrenal axis to l -DOPA; (2) a paradoxical response of the pituitary-adrenal axis to l -DOPA; or (3) a subtle pituitary-adrenal dysfunction.