Adrenal insufficiency causes life-threatening arrhythmia with prolongation of QT interval

Komuro, Jin; Kaneko, Mitsunobu; Ueda, Kazutaka; Nitta, S; Kasao, Masashi; Shirai, Tomoyuki

doi:10.1007/s00380-015-0660-6

Cited by 13 publications

(4 citation statements)

References 9 publications

(10 reference statements)

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“…Clinical data on cardiac electrical activity in patients with AI are scanty. Prolonged QT interval and life-threating arrhythmias, mainly due to electrolytes imbalance, have been reported in few case reports [39][40][41]. In our study, 24 h Holter-ECG was performed in patients with primary and secondary AI without recording any 2).…”

Section: Discussionmentioning

confidence: 87%

Patients with adrenal insufficiency have cardiovascular features associated with hypovolemia

et al. 2020

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Context Patients with adrenal insufficiency (AI) have excess mortality and morbidity, mainly due to cardiovascular (CV) diseases. The mechanisms for this is unclear. Objective To assess CV structure and function in AI patients on conventional replacement therapy and after switching to once-daily, modified-release hydrocortisone (OD-HC) in comparison with healthy matched controls. Methods This was a retrospective analysis of 17 adult AI patients (11 with primary AI, 6 with secondary AI) on stable replacement with cortisone acetate [median (minimum, maximum) 33.5 (12.5–50) mg] and, if needed, fludrocortisone [0.1 (0.05–0.2) mg], and 17 healthy matched controls. Ten patients were switched to an equivalent dose of OD-HC. Data from echocardiography, 24 h Holter-ECG and 24 h blood pressure monitoring were collected at baseline and 6 months after the switch to OD-HC. Results At baseline, AI patients had smaller left ventricular diastolic diameter (47.1 ± 4.2 vs. 51.6 ± 2.3 mm; P = 0.001) and left atrial diameter (34.9 ± 4.7 vs. 38.2 ± 2.6 cm; P = 0.018), and a higher ejection fraction (62.5 ± 6.9% vs. 56.0 ± 4.7%; P = 0.003) than controls. AI patients had lower nocturnal systolic and diastolic blood pressure than controls (108 ± 15 mmHg vs. 117 ± 8 mmHg; P = 0.038 and 65 ± 9 mmHg vs. 73 ± 7 mmHg; P = 0.008, respectively). After the switch to OD-HC, nocturnal diastolic blood pressure normalised. No significant changes were observed in echocardiographic and Holter-ECG parameters following the switch. Conclusions AI patients on conventional treatment display cardiovascular abnormalities that could be related to hypovolemia. Switch to OD-HC seems to have beneficial effect on blood pressure profile, but no effect on cardiovascular structure and function.

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Section: Discussionmentioning

confidence: 87%

Patients with adrenal insufficiency have cardiovascular features associated with hypovolemia

et al. 2020

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“…Building on these findings may also help explain the increased arrhythmia burden reported in human conditions of cortisol excess 93 or deficiency. 94 …”

Section: Discussionmentioning

confidence: 99%

Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility

Tikhomirov,

Oakley,

Anderson

et al. 2024

Circulation Research

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RATIONALE: Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the early morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs and the underlying mechanisms are not understood. OBJECTIVE: The objectives are to investigate the recruitment of transcription factors to time-of-day differentially accessible chromatin that underpins day-night ion channel rhythms and to assess the significance of this for the heart’s day-night rhythm in VA susceptibility. METHODS AND RESULTS: Assay for transposase-accessible chromatin with sequencing performed in mouse ventricular myocyte nuclei at the beginning of the inactive (zeitgeber time, time of lights on, start of sleep period) and active (time of lights off, start of awake period [ZT12]) periods revealed differentially accessible chromatin sites annotating to rhythmically transcribed ion channels and transcription factor binding motifs in these regions. Notably, motif enrichment for the glucocorticoid receptor (GR; transcriptional effector of corticosteroid signaling) binding site in open chromatin profiles at ZT12 was observed, in line with the well-recognized ZT12 peak in circulating corticosteroids. Molecular, electrophysiological, and in silico biophysically detailed modeling approaches demonstrated GR-mediated transcriptional control of ion channels (including Scn5a underlying the cardiac Na + current, Kcnh2 underlying the rapid delayed rectifier K + current, and Gja1 responsible for electrical coupling) and their contribution to the day-night rhythm in the vulnerability to VA. Strikingly, both pharmacological block of GR and cardiomyocyte-specific genetic knockout of GR blunted or abolished ion channel expression rhythms and abolished the ZT12 susceptibility to pacing-induced VA in isolated hearts. CONCLUSIONS: Our study registers a day-night rhythm in chromatin accessibility that accompanies diurnal cycles in ventricular myocytes. Our approaches directly implicate the cardiac GR in the myocyte excitability rhythm and mechanistically link the ZT12 surge in glucocorticoids to intrinsic VA propensity at this time.

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“…HYPOTENSION was also strongly linked to adrenal insufficiency (785) as well as CIR-CULATORY COLLAPSE (756). Patients with adrenal insufficiency have been shown to be at increased risk to lethal arrhythmias when exposed to excessive stress [63].…”

Section: Discussionmentioning

confidence: 99%

Death as a Drug Side Effect in FAERS: Is Glyphosate Contamination a Factor?

Seneff¹,

Swanson²,

Li³

et al. 2015

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An analysis of selected datasets from the FDA's drug Adverse Event Reporting System (FAERS) leads us to hypothesize that glyphosate contamination in both food and drugs is a major contributor to chronic and acute kidney failure respectively. In chronic kidney failure, glyphosate-induced pancreatitis results in the release of trypsin, causing a leaky vasculature. The albumin-bound glyphosate escapes into the tissues, protecting the circulatory system and kidneys but resulting in multiple symptoms related to skin, gut, brain, bones, lungs, etc. The rare and poorly understood acute kidney failure response reported for protamine sulfate and Trasylol ® is strikingly similar to that associated with glyphosate poisoning. Both drugs are derived from biological tissues that are plausibly contaminated with glyphosate. These drugs protect from haemorrhage, which leads to retention of glyphosate in the vasculature, are followed by circulatory collapse and a high likelihood of death as an outcome. We support our argument by comparing symptom profiles of selected subsets of FAERS with those related to glyphosate poisoning, anomalous reactions to protamine sulfate, and conditions showing strong statistical time-trend correlations with glyphosate.

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Adrenal insufficiency causes life-threatening arrhythmia with prolongation of QT interval

Cited by 13 publications

References 9 publications

Patients with adrenal insufficiency have cardiovascular features associated with hypovolemia

Patients with adrenal insufficiency have cardiovascular features associated with hypovolemia

Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility

Death as a Drug Side Effect in FAERS: Is Glyphosate Contamination a Factor?

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