Effect of corticotrophin-releasing hormone on arginine vasopressin and atrial natriuretic factor in patients with Cushing's disease

OBJECTIVE: To evaluate the effect of CRH administration on plasma AVP and ANF concentration in patients with Cushing's disease and healthy subjects. SUBJECTS: Fifteen patients with Cushing's disease and 15 sex- and age-matched healthy subjects entered the study. STUDY DESIGN: All subjects were randomly given i.v. 100 micrograms hCRH and placebo (NaCl 0.9%) on two non consecutive days. Blood samples for plasma AVP and ANF assay were taken before and every 15 min for 2 hr after CRH or placebo. Five out of the 15 patients with Cushing's disease underwent a repeat CRH test after surgical cure of the disease. RESULTS: At baseline evaluation, plasma ANF concentrations were significantly higher in patients with Cushing's disease compared to healthy subjects (15.0 +/- 0.8 vs 10.8 +/- 0.6 pmol/l, P < 0.001) whereas plasma AVP concentrations were similar between the two groups of subjects (8.0 +/- 0.4 vs 6.8 +/- 0.6 pmol/l). CRH administration induced a significant increase in plasma ANF concentrations both in patients with Cushing's disease (24.0 +/- 1.6 pmol/l, P < 0.05) and healthy subjects (29.4 +/- 1.5 pmol/l, P < 0.05). Conversely, a significant increase in plasma AVP concentrations was found only in patients with Cushing's disease (14.7 +/- 1.4 vs 8.0 +/- 0.4 pmol/l, P < 0.05). In addition, patients with Cushing's disease had an increase in ANF levels after CRH significantly lower than that observed in healthy subjects (peak/basal ratio: 1.7 +/- 0.1 vs 3.1 +/- 0.4, P < 0.01). In 5 patients re-tested after disease cure, CRH administration significantly increased plasma ANF levels (26.8 +/- 1.1 vs 10.7 +/- 0.4 pmol/l, P < 0.05) but it did not modify plasma AVP levels (8.4 +/- 0.4 vs 7.3 +/- 0.5 pmol/l). ANF response to CRH in patients cured from Cushing's disease was similar to that recorded in healthy subjects (peak/basal ratio: 2.6 +/- 0.2 vs 3.1 +/- 0.4). CONCLUSION: CRH stimulates ANF secretion both in patients with Cushing's disease and healthy subjects. Plasma ANF response to CRH is blunted in patients with Cushing's disease compared to patients cured from Cushing's disease and healthy subjects, probably because of hypercortisolism. By contrast, CRH stimulates AVP secretion only in patients with Cushing's disease, but not in patients cured from Cushing's disease and healthy subjects. This phenomenon could be related to the activity of the disease.