Plasma atrial natriuretic factor levels in the inferior petrosal sinus blood of patients with Cushing's disease before and after corticotropin-releasing hormone administration

Abstract

Atrial natriuretic factor (ANF) was suggested to be involved as neurohormone in the modulation of hypothalamus-pituitary-adrenal axis in humans. However, this role is still controversial and widely discussed. In order to evaluate whether ANF is secreted in the hypothalamus-pituitary system in humans, plasma ANF concentrations were assayed in samples collected in the inferior petrosal sinus (IPS) blood of patients subjected to IPS sampling for diagnostic purposes or neurosurgical indications. In this retrospective study were included 22 patients: 10 with Cushing's disease (CD) and 12 patients with GH or PRL-secreting pituitary adenoma, used as control group. In the patients with CD, plasma ANF concentration was also assayed after CRH test (hCRH 100 micrograms as i.v. bolus with blood samples after 5, 10 and 15 min). Both in patients with CD and in patients with GH- or PRL-secreting pituitary adenoma, no significant difference was found in plasma ANF levels between IPS ipsilateral (13.0 +/- 1.5 and 12.2 +/- 1.2 pmol/l) or controlateral (13.0 +/- 1.6 and 12.2 +/- 1.4 pmol/l) to the adenoma and peripheral blood (14.2 +/- 2.0 and 13.7 +/- 1.5 pmol/l, respectively). Similarly, no difference was found between the IPS ipsilateral and controlateral to the adenoma in both groups of patients. In patients with CD, CRH administration induced a significant increase of ACTH levels (periphery: 34.9 +/- 6.2 vs 11.5 +/- 2.3 pmol/l, p < 0.05) but it did not induce any significant change of plasma ANF levels (14.0 +/- 2.0 vs 13.4 +/- 1.4 pmol/l in the ipsilateral IPS and 13.4 +/- 1.6 vs 13.4 +/- 1.5 pmol/l in the ipsilateral IPS and 13.4 +/- 1.6 vs 13.4 +/- 1.5 pmol/l in the contralateral IPS). In conclusion, the lack of ANF concentration gradient between IPS and peripheral blood, the lack of any difference in ANF concentrations between patients with CD and acromegalics or hyperprolactinemics and the absence of ANF response to CRH administration do not support the hypothesis of a role for ANF as neurohormone involved in the hypothalamus-pituitary control and particularly in the hypothalamus-pituitary-adrenal axis modulation in humans.