Impact of Conducting Adrenal Venous Sampling in the Morning Versus Afternoon in Primary Aldosteronism

Mau Yoneda; Mitsuhiro Kometani; Ko Aiga; Shigehiro Karashima; Mikiya Usukura; Shunsuke Mori; Yoshimichi Takeda; Daisuke Aono; Seigo Konishi; Kenichiro Okumura; Takahiro Ogi; Satoshi Kobayashi; Yoshiyu Takeda; Takashi Yoneda


J Endo Soc. 2023;7(3) 

In This Article

Abstract and Introduction


Context: Adrenal venous sampling (AVS) is the gold standard technique for subtype differentiation of primary aldosteronism (PA) and to obtain aldosterone and cortisol measurements; however, their secretion patterns show fluctuations during the day.

Objective: We aimed to examine the effects of AVS timing on AVS results.

Methods: This multicenter, retrospective, observational study included a total of 753 patients who were diagnosed with PA and underwent AVS in 4 centers in Japan. Among them, 504 and 249 patients underwent AVS in the morning (AM-AVS) and in the afternoon (PM-AVS), respectively. The outcome measures were the impact of AVS timing and hormone fluctuations in a day on AVS results.

Results: There were no differences in the success rate of AVS, diagnostic rate of disease type, or frequency of discrepancy in PA subtypes between the AM-AVS and PM-AVS groups. Regarding patients with unilateral PA, aldosterone concentrations in adrenal venous blood did not differ between the 2 groups on the dominant or nondominant side. Conversely, regarding patients with bilateral PA, aldosterone concentrations in adrenal venous blood were significantly higher in the AM-AVS than in the PM-AVS group.

Conclusions: The timing of AVS did not seem to have a significant impact on subtype diagnosis. The aldosterone levels in adrenal venous blood were significantly higher in patients with bilateral PA in the AM-AVS group, but there was no such difference between patients with unilateral PA in the AM-AVS and PM-AVS groups. Each subtype may have a different hormone secretion pattern in a day.


Primary aldosteronism (PA) requires appropriate diagnosis and treatment as it is associated with a higher frequency of cerebral and cardiovascular complications than essential hypertension in patients of similar ages and with similar blood pressure levels.[1] Additionally, in previous studies, higher prevalence rates of obesity sleep apnea syndrome and impaired glucose tolerance have been reported among patients with PA than among patients with essential hypertension.[2] Although PA is partly characterized by hypokalemia, recent reports have shown a high frequency of normokalemia among patients with PA,[3] making it difficult to differentiate it from essential hypertension. For these reasons, the clinical practice guideline of the Japan Endocrine Society recommends PA screening for all patients with hypertension. Patients with resistant hypertension are particularly recommended to undergo PA screening as it may be more cost-effective than lifelong medications.[2]

Furthermore, the frequency of PA is estimated to be 3% to 10% in the population with hypertension;[4–6] therefore, it is considered a common disease. Treatment strategies include therapy with mineralocorticoid receptor antagonists or surgery, depending on the PA subtype.[7,8]

The most common procedure for determining the PA subtype is adrenal venous sampling (AVS), wherein blood is drawn directly from the vicinity of the adrenal gland using a catheter and the levels of cortisol and aldosterone secreted by the adrenal cortex are measured. Cortisol is regulated by adrenocorticotropic hormone (ACTH), which is secreted by the anterior pituitary gland. The cortisol level is generally the highest upon awakening and gradually declines over the course of the day. Chan and Debono found that in 33 healthy individuals who underwent 20-min cortisol profiling over a 24-hour period, the cortisol levels were the lowest around midnight, began to rise at around 2:00 to 3:00, and peaked at around 8:30.[9] Aldosterone, similar to cortisol, is also regulated by ACTH and shows diurnal fluctuations, being the highest in the early morning and low in the late evening.[10] Thosar et al showed that the aldosterone levels in healthy individuals exhibit a significant endogenous rhythm, rising at night and peaking in the morning.[11] They also found that this early morning increase in aldosterone is attributed to circadian rhythms and increased morning activity, and it is not caused by presleep inactivity associated with sleep. Other factors that can cause aldosterone levels to fluctuate include body position, salt intake, aging, sex hormones, and medications.

AVS is an invasive and challenging test; however, because of the high frequency of PA, it is currently performed at many institutions in Japan. AVS is generally performed during exogenous ACTH administration, in other words ACTH loading, to improve the success rate of the procedure.[12] However, AVS is also performed before and after ACTH loading. Considering the effects of diurnal variations in the levels of aldosterone and cortisol, the Endocrine Society guidelines recommend that AVS without ACTH loading should be performed in the morning.[13] However, owing to staffing issues and general limitations, AVS is performed in the afternoon in many facilities. Importantly, the impact of AVS timing has not been adequately studied to date. In this study, we examined the effects of AVS timing (morning/afternoon) on hormone secretion of the adrenal gland, as it is well known that cortisol level shows diurnal fluctuations and is elevated by stress. Furthermore, we evaluated the effect of AVS timing on PA diagnosis. The results of our evaluation of the impact of AVS timing could help more facilities to accurately diagnose patients with PA and help clarify the pathogenesis of each form of PA.