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

<p>Abstract</p> <p>Background</p> <p>Increasing 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.</p> <p>Methods/design</p> <p>Overall, 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.</p> <p>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.</p> <p>Discussion</p> <p>In 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.</p> <p>Trial registration</p> <p>ISRCTN33941607</p

Scheme of hepato-splanchinc contribution for hemodynamic stability.

<p>Splanchnic vasoconstriction reduces arterial inflow (black arrows) thereby lowering downstream distending pressures and mobilizing blood volume (white arrows) sequestered in the compliant splanchnic vasculature. At the same time reduced portal vein flow draining form splanchnic vascular beds (purple) causes a compensatory increase (red arrow) in the separate hepatic arterial blood flow (red) because of compensatory vasodilation in Mall´s space.</p

Time course of hepato-splanchnic hemodynamics.

<p>Time course of splanchnic vascular resistance index (<i>RI</i>) (top panel) and hepato-splanchnic perfusion index (<i>QI</i>) (bottom panel) measured at times <i>t</i>₁ through <i>t</i>₄ during dialysis in diabetic (red symbols) and non-diabetic (green symbols) subjects. Symbols represent average values ± standard deviations of duplicate measurements obtained in treatments separated by one week. For clarity, symbols for diabetics and non-diabetics are placed with a small left or right offset from the actual measuring times.</p

Hepato-splanchnic perfusion and resistance.

<p>Splanchnic perfusion index (<i>QI</i>) as function of hepato-splanchnic resistance index (<i>RI</i>) (top panel) and hepato-splachnic vascular conductance (bottom panel), respectively, during hemodialysis, in diabetic (red symbols) and non-diabetic (green symbols) subjects. Broken lines indicate the best fit of <i>QI</i> to <i>RI</i> (top panel, <i>y</i> = 6.71/<i>x</i>, <i>r</i>² = 0.77) and 1/<i>RI</i> (bottom panel, <i>y</i> = 0.02+6.54<i>x</i>, <i>r</i>² = 0.77), respectively.</p