Aldosterone and Parathyroid Hormone: A Complex and Clinically Relevant Relationship

Pilz, Stefan; Tomaschitz, Andreas; März, Winfried; Cavalier, Étienne; Ritz, Eberhard

doi:10.1007/s00223-010-9409-5

Cited by 19 publications

(12 citation statements)

References 19 publications

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“…11, 44 Although we did not measure serum parathyroid hormone in our study, mean serum adjusted calcium was significantly lower in patients with PA (2.37 mmol/L versus 2.47 mmol/L P<0.006), which supports this intriguing hypothesis.…”

Section: Discussionsupporting

confidence: 51%

Demonstration of Blood Pressure-Independent Noninfarct Myocardial Fibrosis in Primary Aldosteronism

Freel

Mark

Weir

et al. 2012

Circ: Cardiovascular Imaging

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Background-Primary aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy in humans and animals possibly mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in human subjects with PA and essential hypertension using contrast-enhanced cardiac magnetic resonance imaging as well as explore the mechanistic basis for any observed differences. Methods and Results-Twenty-seven subjects with recently diagnosed PA and 54 essential hypertension controls were recruited. Subjects underwent gadolinium-enhanced cardiac magnetic resonance; noninfarct related myocardial fibrosis was identified by a diffuse pattern of late gadolinium enhancement. Patients also underwent assessment of pulse wave velocity, measurement of circulating superoxide anion and C-reactive protein, as well as blood pressure and biochemical assessment. Subjects were well matched with no difference in severity or duration of hypertension. There was a significant increase in the frequency of noninfarct late gadolinium enhancement in PA (70%) when compared with essential hypertension subjects (13%; P<0.0001) with no difference in left ventricular mass. Pulse wave velocity, superoxide, and C-reactive protein were significantly higher in subjects with PA. Conclusions-These data illustrate that patients with PA exhibit frequent myocardial fibrosis as demonstrated by late gadolinium enhancement using cardiac magnetic resonance imaging; this finding is independent of blood pressure. This may be mediated partly through inflammation and oxidative stress. This study highlights the importance of specific targeting of aldosterone excess as well as blood pressure reduction to minimize cardiac morbidity in PA. (Circ Cardiovasc Imaging. 2012;5:740-747.)

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Section: Discussionsupporting

confidence: 51%

Demonstration of Blood Pressure-Independent Noninfarct Myocardial Fibrosis in Primary Aldosteronism

Freel

Mark

Weir

et al. 2012

Circ: Cardiovascular Imaging

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“…Obesity has been linked to a shift in the 25(OH)D-PTH relationship 43 ; however, acute changes in PTH were observed using within-individual comparisons. We present possible explanations to account for a direct mechanism behind the RAAS-mediated effects we observed; however, calcium modulation has been implicated as potential indirect mediator of RAAS-PTH interactions 12 , and we did not have detailed electrolyte assessment, including magnesium and ionized and urinary calcium in all of our protocols. Of note, prior studies failed to show any modulation in ionized calcium with the AngII infusion doses we used 35 , thereby supporting a possible direct AngII-mediated effect on PTH, as we propose.…”

Section: Discussionmentioning

confidence: 98%

“…Calcium 1,2 , vitamin D 3–9 , and parathyroid hormone (PTH) 10–12 have been implicated in regulating the renin-angiotensin-aldosterone system (RAAS), and the RAAS, in turn, has been implicated in regulating these calcium-regulatory hormones 13–16 . In particular, recent observational studies in individuals with primary hyperaldosteronism (PA) suggest that excess aldosterone may result in hyperparathyroidism 15–17 .…”

Section: Introductionmentioning

confidence: 99%

Human Interventions to Characterize Novel Relationships Between the Renin–Angiotensin–Aldosterone System and Parathyroid Hormone

et al. 2014

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Observational studies in primary hyperaldosteronism (PA) suggest a positive relationship between aldosterone and parathyroid hormone (PTH); however, interventions to better characterize the physiologic relationship between the renin-angiotensin-aldosterone system (RAAS) and PTH are needed. We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without PA. PTH was measured before and after: Study 1) low-dose angiotensin II [AngII] infusion (1 ng/kg/min) and captopril administration (25 mg × 1); Study 2) high-dose AngII infusion (3 ng/kg/min); Study 3) blinded crossover randomization to aldosterone infusion (0.7 µg/kg/hr) and vehicle; and Study 4) blinded randomization to spironolactone (50mg/daily) or placebo for 6 weeks. Infusion of AngII at 1 ng/kg/min acutely increased aldosterone (+148%) and PTH (+10.3%), while AngII at 3 ng/kg/min induced larger incremental changes in aldosterone (+241%) and PTH (+36%) (P<0.01). Captopril acutely decreased aldosterone (−12%) and PTH (−9.7%) (P<0.01). In contrast, aldosterone infusion robustly raised serum aldosterone (+892%) without modifying PTH. However, spironolactone therapy over 6 weeks modestly lowered PTH when compared to placebo (P<0.05). In vitro studies revealed the presence of AngII type I and mineralocorticoid receptor mRNA and protein expression in normal and adenomatous human parathyroid tissues. We observed novel pleiotropic relationships between RAAS components and the regulation of PTH in individuals without PA: the acute modulation of PTH by the RAAS appears to be mediated by AngII, whereas the long-term influence of the RAAS on PTH may involve aldosterone. Future studies to evaluate the impact of RAAS inhibitors in treating PTH-mediated disorders are warranted.

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“…Accumulating evidence points to the bidirectional interplay between PTH and aldosterone as an important mechanism behind the increased risk of CV damage observed in PHPT [9,10]. Experimental and clinical data support the notion that PTH directly stimulates adrenal steroid secretion by inducing calcium entry in adrenal ZG cells via binding to PTH/PTH-related protein receptor (PTH/PTHrP receptor = PTH1R), voltage-gated L-type calcium channels and by activating various signal transduction pathways [11,12].…”

Section: Introductionmentioning

confidence: 99%

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

et al. 2012

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BackgroundIncreasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess.Methods/designOverall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease.The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1–84) as the primary endpoint and (2) 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints.DiscussionIn view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism.Trial registrationISRCTN33941607

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Aldosterone and Parathyroid Hormone: A Complex and Clinically Relevant Relationship

Cited by 19 publications

References 19 publications

Demonstration of Blood Pressure-Independent Noninfarct Myocardial Fibrosis in Primary Aldosteronism

Demonstration of Blood Pressure-Independent Noninfarct Myocardial Fibrosis in Primary Aldosteronism

Human Interventions to Characterize Novel Relationships Between the Renin–Angiotensin–Aldosterone System and Parathyroid Hormone

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

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