Effect of atrial natriuretic factor infusion on basal and CRH-stimulated ACTH, cortisol and aldosterone levels in patients with Cushing's or Addison's disease.
OBJECTIVE
While it has been shown that atrial natriuretic factor (ANF) is able to inhibit CRH-stimulated ACTH secretion in vitro, in normal men conflicting results on its effect on ACTH/cortisol responses to insulin and CRH have been reported. Since no data are available concerning the possible influence of ANF on the hypothalamic-pituitary-adrenal axis in states of ACTH hypersecretion, the effect of ANF on pituitary-adrenal function in basal conditions and after CRH stimulation has been investigated in patients with Cushing's (n = 4) and Addison's disease (n = 4).


METHODS
On two different days all patients underwent the following procedures: (a) alpha-human ANF was infused, after a priming dose of 100 ng i.v., at a rate of 0.01 microgram/kg/min over 5 hours. After 120 minutes of ANF infusion, oCRH (1 microgram/kg) was i.v. injected as a bolus; (b) vehicle infusion was given over 5 hours and at 120 minutes oCRH was injected. Plasma ANF, ACTH, cortisol, aldosterone, renin activity and K+ were measured; heart rate and blood pressure were monitored.


RESULTS
In Cushing's disease plasma ANF rapidly increased within 30 minutes of the exogenous peptide infusion (from 27 +/- 5 to 73 +/- 14 pmol/l; mean +/- SE), whereas in the vehicle study its concentration was unchanged. During the first 2 hours of both tests no significant modifications in ACTH levels were observed. After CRH the plasma ACTH peak was unchanged. Serum cortisol levels progressively declined during the first 2 hours of ANF infusion (from 778 +/- 150 to 461 +/- 48 nmol/l; P < 0.05), whereas no changes were observed during vehicle. After CRH serum cortisol rose to similar peaks. Plasma aldosterone levels were significantly reduced during the first 2 hours of ANF infusion (from 81 +/- 20 to 35 +/- 7 pmol/l P < 0.05), whereas no changes were found during vehicle. A similar aldosterone rise was induced by CRH during either vehicle or ANF. Mean plasma renin activity slightly declined and the changes were similar on both occasions. In Addison's disease ANF levels rose within 30 minutes of the peptide infusion (from 12 +/- 1 to 49 +/- 8 pmol/l), while they were unchanged during vehicle. A slight decline in ACTH levels in the first 2 hours was observed during either vehicle or ANF infusion. After CRH the plasma ACTH peaks were similar. Mean plasma renin activity was unaffected by vehicle, while ANF caused a decline during the first 2 hours (from 13.4 +/- 0.8 to 7.7 +/- 0.3 ng/ml/h). In all patients, heart rate, blood pressure and K+ were only slightly affected on both occasions.


CONCLUSIONS
(1) In patients with corticotrophin hypersecretion ANF does not influence basal and CRH-stimulated ACTH secretion; (2) in Cushing's disease ANF inhibits cortisol and aldosterone basal secretion; this effect is not mediated by ACTH and is over-ridden by CRH stimulation.
Istituti di Scienze Endocrine, Università di Milano, Ospedale Maggiore IRCCS, Italia.
B
B
Ambrosi
C
C
Sala
D
D
Bochicchio
P
P
Colombo
G
G
Gazzano
C
C
Fadin
A
A
Morganti
G
G
Faglia
D000224:Addison Disease / Q000097:blood*; D000305:Adrenal Cortex Hormones / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003480:Cushing Syndrome / Q000097:blood*; D003864:Depression, Chemical; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone