Role of endogenous ACTH on circadian aldosterone rhythm in patients with primary aldosteronism

Abstract

We recently reported that stimulation with high-dose ACTH caused different responses in terms of aldosterone secretion in aldosterone-producing adenomas (APAs) and idiopathic hyperaldosteronism (IHA) in patients with primary aldosteronism (PA). However, the role of endogenous ACTH in aldosterone secretion in PA has not been systematically evaluated. In this study, we examined diurnal changes in plasma aldosterone concentration (PAC), and changes in PAC after dexamethasone administration in patients with suspected PA, in order to evaluate the effect of endogenous ACTH on aldosterone secretion. Seventy-three patients admitted to Kyoto University Hospital with suspected PA were included. The patients were classified into non-PA, IHA, and APA groups according to the results of captopril challenge test and adrenal venous sampling. PAC at 0900 h (PAC 0900 ), 2300 h (PAC 2300 ), and after 1-mg dexamethasone suppression test (PAC dex ) was measured and compared among the three groups. The PAC 2300 /PAC 0900 and PAC dex /PAC 0900 ratios were also analyzed. PAC 2300 and PAC dex were lower than PAC 0900 in all three groups. There were no significant differences in PAC 2300 /PAC 0900 among the three groups. However, PAC dex /PAC 0900 was significantly lower in the APA group compared with the non-PA and IHA groups. The results of this study indicate that aldosterone secretion in APA patients is more strongly dependent on endogenous ACTH than in IHA and non-PA patients. The results also suggest that factors other than ACTH, such as clock genes, may cause diurnal changes in aldosterone secretion in IHA and non-PA patients.

Subtype prediction in primary aldosteronism: measurement of circadian variation of adrenocortical hormones and 24‐h urinary aldosterone

“…This suggests that aldosterone secretion in APA patients is more strongly dependent on endogenous ACTH than in IHA patients. [14][15][16][17] Indeed, aldosterone synthesis and secretion are regulated by ACTH stimulation, 18,19 and aldosterone secretion stimulated by ACTH via the ACTH receptor (MC2R) occurs by a coupled interaction between cAMP and Ca 2+ pathways as an acute secretion process. [18][19][20][21] Importantly, some reports have showed that MC2R overexpression is mainly observed in APA.…”

Aldosterone-Regulating Receptors and Aldosterone-Driver Somatic Mutations

“…In contrast with angiotensin II and potassium, ACTH stimulates aldosterone secretion acutely but transiently ( 31 , 47 ). Aldosterone production follows a circadian rhythm that parallels that of ACTH both in normal individuals, as well as in patients with PA ( 48 , 49 ). In patients with aldosterone-secreting tumors, plasma aldosterone concentration starts to fall around mid-morning, as ACTH levels decrease, in spite of upright posture ( 39 ).…”

“…The relative impact of ACTH on aldosterone production from APA vs. BHA and normal ZG cells remains incompletely understood. Small studies suggest that APAs might be more sensitive to ACTH stimulation and suppression than BHA and normal adrenals ( 49 ). Asian studies ( 50 – 52 ) indicated that the response of aldosterone to cosyntropin stimulation, with or without a priori overnight suppression with 1mg dexamethasone, is higher in patients with APA than in those with BHA.…”

Role of adrenocorticotropic hormone in essential hypertension and primary aldosteronism

“…Moreover, they reported that ACTH administration produced higher aldosterone concentrations in patients with PA compared with normal controls or patients with essential hypertension . Diurnal increase of aldosterone in early morning and abolition of diurnal rhythm by dexamethasone confirms the role of endogenous ACTH as an important aldosterone secretagogue in PA . Of note, Kobayashi and colleagues showed that early morning systolic BP was correlated with ACTH .…”