Background: Aldosterone production can be regulated by adrenocorticotrophic hormone (ACTH) which normally controls cortisol secretion. Some cases of aldosterone-producing adenoma (APA) display features which may suggest increased sensitivity to the stimulatory effects of ACTH.
Aim: To investigate if there is any relationship between the hypothalamic-pituitary-adrenocortical axis (HPA) activity and the characteristics of APAs.
Methods: This is a retrospective review involving 41 histologically-confirmed APA cases which were characterised with regards to clinical, biochemical and somatic mutation status. HPA activity was assessed from morning plasma cortisol, ACTH and 1mg overnight dexamethasone (DEX) suppression test. Correlation was analysed by Pearson’s correlation coefficient, and the HPA activity between APAs with KCNJ5 mutation and those without was compared using Mann Whitney U-test.
Results: Twelve out of 41 patients (29.3%) were women, median age was 49 years and 85.4% were overweight/obese. All except 2 had somatic mutations within APA. Fourteen (34.1%) were KCNJ5 mutation. Only one patient (not KCNJ5-mutated) had post-DEX cortisol >50 nmol/L. Upright morning plasma aldosterone concentration (PAC) correlated with tumour size (r=0.347, P=0.026), plasma cortisol (r=0.425, P=0.006) and plasma ACTH (r=0.446; P=0.056). Plasma ACTH and cortisol were positively correlated (r=0.511, P=0.025). Higher PAC, cortisol and ACTH concentrations were in turn associated with the need for higher defined-daily-dose of anti-hypertensives (r=0.466, P=0.002 for PAC; r=0.315, P=0.045 for cortisol; r=0.449, P=0.054 for ACTH). Higher PAC was also predictive of higher BMI (r=0.348, P=0.026). Plasma cortisol, ACTH, post-DEX cortisol, BMI and anti-hypertensives dose were not significantly different between those with KCNJ5 mutation vs those without.
Conclusions: HPA activity correlated with clinico-biochemical characteristics in patients with APAs, but the prevalence of autonomous hypercortisolism was low. The findings suggest a potential role of ACTH in the pathophysiology of APAs. There was no significant difference in HPA activity between those with somatic KCNJ5 mutation compared to those without.