Circadian Rhythm of Plasma Aldosterone Concentration in Patients with Primary Aldosteronism

Kem, David C.; Weinberger, Myron H.; Gómez-Sánchez, Celso E.; Kramer, Norman J.; Lerman, Robert H.; Furuyama, Shunsuke; Nugent, Charles A.

doi:10.1172/jci107414

Cited by 120 publications

(35 citation statements)

References 25 publications

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“…PAC was suppressed more strongly by 1 mg dexamethasone in the APA group than in the non-PA and IHA groups, indicating a greater dependency of aldosterone secretion on endogenous ACTH in APA patients compared with IHA and non-PA patients. These results are in accordance with previous studies (12,13,14,15).…”

Section: Discussionsupporting

confidence: 94%

“…Previous reports documented a diurnal decline in PAC, and a decline in PAC following dexamethasone administration in PA and essential hypertensive patients (13,14,15), but these reports only analyzed a small number of cases and the selection of patients was not systematic, resulting in a risk of selection bias. Therefore, the role of endogenous ACTH on aldosterone secretion in patients with PA has not been clearly defined.…”

Section: Introductionmentioning

confidence: 99%

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

Sonoyama

Sone

Tamura

et al. 2015

EJEA

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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.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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

Sonoyama

Sone

Tamura

et al. 2015

EJEA

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“…Herein, the circardian rhythm of salivary aldosterone was assessed on an outpatient basis on a large cohort for the first time, and the results are similar to plasma measurements in primary hyperaldosteronism published earlier [15,16]. The profiles mirror well the typical diurnal rhythm of plasma aldosterone, with the highest concentrations in the morning hours, which gradually decline throughout the day.…”

Section: Salivary Aldosterone Profilingsupporting

confidence: 58%

The Clinical Value of Salivary Aldosterone in Diagnosis and Follow-Up of Primary Aldosteronism

et al. 2016

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Primary aldosteronism (PA), the most common form of secondary hypertension, causes relevant morbidity. The value of salivary measurements of aldosterone in clinical routine in PA so far has not been assessed. First, we analyzed salivary and plasma aldosterone concentrations of 42 patients with PA and 37 hypertensive controls (HC) during a sodium infusion test prospectively. Second, morning salivary and plasma aldosterone concentrations as well as diurnal saliva aldosterone profiles were analyzed in 115 patients treated for PA (46 adrenalectomy, 56 spironolactone, 13 eplerenone). Salivary aldosterone was substantially elevated in PA patients compared to HC at baseline (106?119 vs. 40?21?ng/l, p=0.01), and after 4-h sodium infusion test (60?36 vs. 23?14, p=0.01). Positive correlation between salivary and plasma aldosterone levels was evident, with exception of concentrations in or below the lower normal range. Applying a salivary aldosterone cutoff of 51.2?ng/l, found by ROC curve analysis, rendered a sensitivity of 81% and a specificity of 73% for PA. The diurnal rhythm of aldosterone was preserved in untreated PA patients, but concentrations were higher in the context of PA, and normalized after surgery (118?57 vs. 31?18?ng/l, p<0.01). Taken together, salivary aldosterone measurements correlate with plasma levels, allowing simple and cost effective assessments of aldosterone secretion in an outpatient setting. Nevertheless, as this method alone cannot replace other plasma parameters, and as aldosterone profiling would not alter diagnostic or treatment strategies, salivary aldosterone measurements in routine practice are of limited clinical value.

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“…In favour of such a potential ACTH effect is the finding that the highest ACTH-R mRNA expression in adrencortical tumours is found in APAs (49,50,51). Indeed, aldosterone secretion, although relatively unresponsive to postural studies in such patients, exhibits an ACTH-dependent diurnal rhythm and responds to dexamethasone suppression (52,53,54). Moreover, the aldosterone response to ACTH-related physical and/or psychological stress has never been investigated in patients with hypertension.…”

Section: Evidence In Favour Of An Acth Role In Aldosterone Regulationmentioning

confidence: 99%

PROGRESS IN ALDOSTERONISM: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension

Piaditis

Markou

Papanastasiou

et al. 2015

European Journal of Endocrinology

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Primary aldosteronism (PA) secondary to excessive and/or autonomous aldosterone secretion from the renin-angiotensin system accounts for w10% of cases of hypertension and is primarily caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenomas (APAs). Although the diagnosis has traditionally been supported by low serum potassium levels, normokalaemic and even normotensive forms of PA have been identified expanding further the clinical phenotype. Moreover, recent evidence has shown that serum aldosterone correlates with increased blood pressure (BP) in the general population and even moderately raised aldosterone levels are linked to increased cardiovascular morbidity and mortality. In addition, aldosterone antagonists are effective in BP control even in patients without evidence of dysregulated aldosterone secretion. These findings indicate a higher prevalence of aldosterone excess among hypertensive patients than previously considered that could be attributed to disease heterogeneity, aldosterone level fluctuations related to an ACTH effect or inadequate sensitivity of current diagnostic means to identify apparent aldosterone excess. In addition, functioning aberrant receptors expressed in the adrenal tissue have been found in a subset of PA cases that could also be related to its pathogenesis. Recently a number of specific genetic alterations, mainly involving ion homeostasis across the membrane of zona glomerulosa, have been detected in w50% of patients with APAs. Although specific genotype/phenotype correlations have not been clearly identified, differential expression of these genetic alterations could also account for the wide clinical phenotype, variations in disease prevalence and performance of diagnostic tests. In the present review, we critically analyse the current means used to diagnose PA along with the role that ACTH, aberrant receptor expression and genetic alterations may exert, and provide evidence for an increased prevalence of aldosterone dysregulation in patients with essential hypertension and pre-hypertension.

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Circadian Rhythm of Plasma Aldosterone Concentration in Patients with Primary Aldosteronism

Cited by 120 publications

References 25 publications

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

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

The Clinical Value of Salivary Aldosterone in Diagnosis and Follow-Up of Primary Aldosteronism

PROGRESS IN ALDOSTERONISM: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension

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