Blood Pressure Profile and N-Terminal-proBNP Dynamics in Response to Intravenous Methylprednisolone Pulse Therapy of Severe Graves' Orbitopathy

Abstract

Hypercortisolemia is associated with increased risk of hypertension. Natural and synthetic glucocorticoids (GCs) have different effects on blood pressure (BP). The effect of synthetic GCs on BP depends on the dose, treatment duration, type of GCs, and route of administration. Intravenous methylprednisolone (IVMP) pulse therapy is the first line of treatment for severe Graves' orbitopathy (GO). The aim of this study was to evaluate influence of IVMP pulses on BP and N-terminal pro-brain natriuretic peptide (NT-proBNP) dynamics. A total of 32 patients with GO were treated with one IVMP pulse every week for 12 weeks. We performed 48-h BP monitoring (24-h before and 24-h after IVMP) and measured NT-proBNP before, 24 h, and 48 h after the 1st, 6th, and 12th IVMP pulse. Mean BP did not change after any of the pulses. We did not observe an increase in maximal systolic BP or mean nocturnal BP, except after the last pulse. Additionally, the dipping phenomenon was less frequent after the last pulse. We found a significant increase in median NT-proBNP levels after all analyzed pulses. Our study suggests that IVMP may have an unfavorable cumulative effect on BP. Variation in NT-proBNP concentration indicates a compensatory effect of brain natriuretic peptide secretion.

Keywords: Graves’ disease; NT-proBNP; ambulatory blood pressure monitoring; blood pressure; glucocorticoids; graves’ orbitopathy; hypertension; methylprednisolone; pulse therapy.

Figure 1

Changes in maximal systolic blood pressure. max SBP is maximal systolic blood pressure (BP), 1-0 is 24-hours (h) before first intravenous methylprednisolone (IVMP) infusion, 1-1 is 24-h after the beginning of first IVMP infusion, 6-0 is 24-h before sixth IVMP infusion, 6-1 is 24-h after the beginning of sixth IVMP infusion, 12-0 is 24-h before 12th IVMP infusion, and 12-1 is 24-h after the beginning of 12th IVMP infusion. The different colors of lines “grey, white, black…” define BP measurements in examined patients.

Figure 2

Changes in mean nocturnal blood pressure. BP is blood pressure, 1-0 is 24-hours (h) before first intravenous methylprednisolone (IVMP) infusion, 1-1 is 24-h after the beginning of first IVMP infusion, 6-0 is 24-h before sixth IVMP infusion, 6-1 is 24-h after the beginning of sixth IVMP infusion, 12-0 is 24-h before 12th IVMP infusion, and 12-1 is 24-h after the beginning of 12th IVMP infusion. The different colors of lines “grey, white, black…” define BP measurements in examined patients.

Figure 3

Changes in NT-proBNP values in the selected points of the study. NT-proBNP—N-terminal pro-brain natriuretic peptide, 1-0: before first intravenous methylprednisolone (IVMP) infusion, 1-24: 24 hours (h) after first IVMP infusion, 6-0: before 6th IVMP infusion, 6-24: 24 h after sixth IVMP infusion, 12-0: before 12th IVMP infusion, 12-24: 24 h after 12th IVMP infusion. The different colors of lines “grey, white, black…” define changes in NT-proBNP values in examined patients.

Figure 4

The scheme of study design. * Evaluation of cardiovascular biomarkers included examination of N-terminal pro-brain natriuretic peptide, troponin I, 24 and 48 h after intravenous methylprednisolone (IVMP) pulse. ** Hemodynamic evaluation included 48-h ambulatory blood pressure monitoring during 24-h before and 24-h after IVMP infusion.