Abstract
Purpose
Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic–pituitary–adrenal (HPA) axis, mediating the ‘‘proactive’’ feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison’s disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated.
Methods
Ten patients affected by autoimmune Addison’s disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy.
Results
H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone.
Conclusions
Our study showed a lack of FC effect on corticotrope secretion in Addison’s disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.
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The authors declare that they have no conflict of interest.
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All the procedures involved in the study were in accordance with the ethical standards of the ethical institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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R. Berardelli and I. Karamouzis contributed equally as first authors.
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Berardelli, R., Karamouzis, I., D’Angelo, V. et al. The acute effect of a mineralocorticoid receptor agonist on corticotrope secretion in Addison’s disease. J Endocrinol Invest 39, 537–542 (2016). https://doi.org/10.1007/s40618-015-0393-5
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DOI: https://doi.org/10.1007/s40618-015-0393-5