Altered Dopaminergic Modulation of 18- Hydroxycorticosterone Secretion in Idiopathic Edema:Therapeutic Effects of Bromocriptine

We have investigated dopaminergic mechanisms involved in the control of corticosteroid secretion in patients with idiopathic edema. The effects of treatment with the dopamine agonist bromocriptine (2.5 mg, three times a day for 5 days) on PRA, plasma cortisol, corticosterone, 18-hydroxycorticosterone (18-OHB), aldosterone, and PRL levels, and blood pressure responses to upright posture and isometric exercise were evaluated in nine patients with idiopathic edema and nine normal controls. Additionally, PRA and plasma cortisol, corticosterone, 18-OHB, aldosterone, and PRL responses to the dopamine antagonist metoclopramide were evaluated in both groups. Basal supine levels of PRA, cortisol, corticosterone, aldosterone, and PRL were similar in the two groups. However, plasma 18-OHB was considerably greater in the edema patients. Edema patients displayed greater orthostatic weight gain and greater 18-OHB and aldosterone responses to upright posture and isometric handgrip exercise. Bromocriptine treatment markedly decreased basal plasma 18-OHB levels and increased plasma corticosterone levels in both groups. Bromocriptine had no effect on PRA or basal supine levels of plasma aldosterone. However, after bromocriptine treatment, these orthostatic responses were similar to those observed in normal controls. After metoclopramide administration, edema patients displayed normal PRA and aldosterone responses, but exaggerated 18-OHB and PRL responses. These results after additional evidence that dopaminergic mechanisms modulate 18-OHB and aldosterone secretion, perhaps by modulating adrenal glomerulosa 18-hydroxylase activity. The results of this study also suggest that idiopathic edema is a disease characterized by decreased tonic dopaminergic modulation of the 18-hydroxylase enzyme, which affects the conversion of corticosterone to 18-OHB. Diminished orthostaticexcretion of sodium in idiopathic edema appears to be related to decreased dopaminergic tone. This abnormality is largely corrected by tolerable doses of the dopamine agonist bromocriptine. (J Clin Endocrinol Metab55:749, 1982)