Primary hyperaldosteronism is associated with derangement in the regulation of the hypothalamus-pituitary-adrenal axis in humans

Hippocampal mineralocorticoid receptors (MR) play a major role in the control of hypothalamus-pituitary-adrenal (HPA) axis. The functional profile of HPA axis and the impact of MR blockade under chronic exposure to mineralocorticoid excess are unknown. To clarify this issue, ACTH, cortisol, and aldosterone secretions were studied in 6 patients with primary hyperalclosteronism (HA) and 8 controls (NS) during placebo, placebo+human CRH (hCRH) (2 pg/kg iv bolus at 22:00 h), potassium canrenoate (CAN, 200 mg iv bolus at 20:00 h followed by 200 mg infused over 4 h) or CAN+hCRH. During placebo, both aldosterone and ACTH levels were higher (p<0.01) in HA than in NS, while cortisol levels were not significantly different. Both HA and NS showed significant ACTH and cortisol responses to hCRH (P<0.004), although the hormonal responses in HA were higher (p<0.02) than in NS. CAN infusion did not modify aldlosterone levels in both HA and NS. Under CAN infusion, ACTH showed progressive rise in NS (p<0.05) but not in HA, while cortisol levels showed a significant (p<0.05) but less marked and delayed increase in HA compared to NS. CAN enhanced hCRH-induced ACTH and cortisol responses in NS (p<0.05), but not in HA. In conclusion, in humans primary hyperaldosteronism is associated with deranged function of the HPA axis. In fact, hyperaldosteronemic patients show basal and hCRH-stimulated HIPA hyperactivity that is, at least partially, refractory to further stimulation by mineralocorticoid blockade with canrenoate. Whether this hormonal alteration can influence the clinical feature of hypertensive patients with primary hyperaldosteronism needs to be clarified.