Dramatic recovery of left ventricular dysfunction in a patient with pseudoaldosteronism, hypokalaemia, and rhabdomyolysis: a case report

Abstract

Background

Excessive liquorice ingestion sometimes causes pseudoaldosteronism. The association between liquorice-induced pseudoaldosteronism and acute heart failure has not been well described.

Case summary

An 89-year-old woman was referred to the hospital due to muscle weakness with rhabdomyolysis and severe hypokalaemia. The electrocardiogram in the emergency department revealed pulseless ventricular tachycardia, thus, emergent defibrillation was delivered. Laboratory findings revealed severe hypokalaemia with metabolic alkalosis. Plasma renin activity and serum aldosterone were highly suppressed. Her medications included herbal medicines containing a great amount of liquorice. The patient was diagnosed with pseudoaldosteronism caused by liquorice over-ingestion. She developed acute pulmonary oedema with unexpected left ventricular (LV) dysfunction after the peak out of creatine kinase. She was managed with acute heart failure therapy, as well as optimal medical therapy. She accidentally developed an acute embolic stroke but fully recovered due to emergent thrombolytic therapy. Cardiac magnetic resonance imaging revealed banding late gadolinium enhancement in the basal-mid segments, which was inconsistent with takotsubo cardiomyopathy. As time passed, LV function unexpectedly improved, and congestive heart failure was completely compensated.

Discussion

Liquorice contains glycyrrhetinic acid that inhibits 11βHSD2. This invites the over-activation of mineralocorticoid receptors by cortisol in the kidneys and eventually causes hypokalaemia and hypertension. Acute heart failure caused by excessive liquorice ingestion is scarcely described. The triggering factors for LV dysfunction and acute congestive heart failure remain unclear. Rhabdomyolysis could affect massive catecholamine release and cause LV dysfunction.

Learning points.

• Since acute left ventricular dysfunction could occur, a patient with pseudoaldosteronism and rhabdomyolysis should be managed by a multidisciplinary team, including a cardiologist.

• Immediate reverse remodelling of left ventricular dysfunction in such patients could be possible, and serial evaluation of left ventricular function is necessary.

Introduction

Many herbal medicines mainly contain liquorice.¹ Pseudoaldosteronism is caused by excessive liquorice ingestion by 11 beta-hydroxysteroid dehydrogenase type 2 (11βHDS2) inhibition, which is an enzyme that converts cortisol to cortisone.² The relationship between primary aldosteronism and cardiovascular disease, including heart failure, is established,³ but the association between liquorice-induced pseudoaldosteronism and acute heart failure was not fully described. Herein, we present a case of acute heart failure concomitant with liquorice-induced pseudoaldosteronism and rhabdomyolysis, highlighting a dramatic recovery of left ventricular (LV) dysfunction despite developing cardiac fibrosis during a short-term clinical course. The current case revealed that LV dysfunction may develop through cardiac fibrosis but might be reversible in pseudoaldosteronism.

Summary figure

Case presentation

An 89-year-old woman (height: 138 cm, weight: 43 kg) with a history of hypertension, dyslipidaemia, and osteoporosis, was referred to our hospital due to a susception of drug-induced rhabdomyolysis. Her medications from two different clinics included eldecalcitol at 0.75 μg, amlodipine at 5 mg, pravastatin at 5 mg, mecobalamin at 500 μg, yokukansan at 7.5 g (containing liquorice at 1.5 g), furosemide at 20 mg, shakuyakukanzoto (containing liquorice at 4 g), limaprost alfadex at 15 μg, lactomin amylolytic bacillus, famotidine at 20 mg, etodolac at 400 mg, and etizolam at 1 mg. She consulted her general physician a day before referral due to a feeling of general fatigue and worsening bilateral upper extremities muscle weakness. Laboratory tests with her general physician revealed severe hypokalaemia (1.8 mEq/L) and elevated CK level (4910 IU/L). Troponin I level was 0.0773 ng/mL, and CK-MB (myoglobin binding) level was 15 IU/L. The patient presented with a blood pressure of 171/80 mmHg and a regular heart rate of 105 b.p.m. during the initial assessment at our emergency department. Electrocardiogram (ECG) revealed frequent premature ventricular contractions (Figure 1) and pulseless ventricular tachycardia, i.e. torsades de pointes; thus, immediate defibrillation was delivered. Transthoracic echocardiography (TTE) demonstrated visually normal LV function (Supplementary material online, Video S1). Further laboratory analysis, including arterial blood gas, revealed severe hypokalaemia (1.7 mEq/L), and metabolic alkalosis (pH: 7.54, partial pressure of carbon dioxide: 51.8 mmHg, partial pressure of oxygen: 62.2 mmHg, and bicarbonate: 43.9 mmol/L), while renal function (serum creatinine: 0.57 mg/dL and serum blood urea nitrogen: 7.0 mg/dL) remained normal. The patient’s CK level was also elevated at 4449 IU/L. Spot urinary potassium concentration was 9.9 mEq/L. Chest X-ray revealed cardiomegaly and mild congestion. Based on the above findings, hypokalaemia with metabolic alkalosis secondary to hyperaldosteronism was suspected. She was hospitalized and managed with aggressive potassium replacement therapy, requiring 140–160 mEq of intravenous potassium chloride daily. Herbal medicines were discontinued. After the admission, blood pressure gradually improved from 140–160/85–100 mmHg to 120–135/85–95 mmHg. Eventually, potassium levels were up to 3.6 mEq/L on Day 4. Plasma renin activity (PRA) and aldosterone levels were both highly suppressed at the presentation [PRA: <0.2 ng/mL/h (0.2–3.9 ng/mL/h), plasma aldosterone: <4.0 pg/mL (4.0–82.1 pg/mL)], thus, pseudoaldosteronism secondary to excessive liquorice intake was indicated.

Figure 1.

Electrocardiogram showing multifocal premature ventricular contraction.

Creatine kinase level elevation progressed through Day 3 (peak CK level of 8492 IU/L, Figure 2), accompanied by acute kidney injury (serum creatinine: 1.41 mg/dL). Creatine kinase-myoglobin binding level was not elevated (Day 2; 8 IU/L, Day 4; 9 IU/L). Furosemide was intravenously administered on Day 4 since congestive kidney was suspected. Chest X-ray on Day 6 revealed cardiomegaly and butterfly shadow with bilateral pleural effusions consistent with pulmonary oedema, and transthoracic echocardiography revealed decreased LV dysfunction [LV ejection fraction (LVEF) of 24% by modified Simpson method, Supplementary material online, Video S2] with no focal wall motion abnormality. The ECG revealed a complete right bundle branch block with a negative T wave in V1–4 leads. Laboratory findings demonstrated an elevated Brain Natriuretic Peptide (BNP) level (2251.1 pg/mL). She was managed with furosemide and dobutamine (1γ) because of decreased estimated stroke volume (18 mL) in TTE. The optimal medical therapy for heart failure with reduced ejection fraction was concomitantly initiated with spironolactone at 50 mg, enalapril at 1.25 mg, and empagliflozin at 10 mg. She developed a hypokalaemia recurrence (2.5 mEq/L) on Day 8, causing paroxysmal atrial fibrillation as aggressive potassium replacement therapy was attenuated. Concurrently, she suddenly developed aphasia, and brain magnetic resonance imaging (MRI) revealed a left middle cerebral artery M1 occlusion, consistent with acute embolic stroke. A tissue plasminogen activator was immediately administered, and emergent cerebral angiography demonstrated almost a complete left middle cerebral artery reperfusion. She completely recovered with no sequelae from acute stroke. The TTE revealed almost complete recovery of LV function (LVEF of 50% by modified Simpson method) on Day 14 and more LV function recovery (LVEF of 59% by modified Simpson method, Supplementary material online, Video S3) on Day 21. The decreased BNP level was demonstrated, commensurate with LVEF recovery. Concurrently, myocardial perfusion scintigraphy revealed no evidence of ischaemia. Cardiac MRI revealed banding late gadolinium enhancement (LGE) in the basal-mid segments (Figure 3). She was symptom-free and got discharged home on Day 25. The clinical course of blood CK, BNP, potassium levels, and LVEF are summarized in Figure 2.

Figure 2.

The clinical course of blood creatinine kinase, brain natriuretic peptide, potassium levels, and left ventricular ejection fraction from admission to discharge. LVEF, left ventricular ejection fraction; CK, creatine kinase.

Figure 3.

Cardiac magnetic resonance image of a sagittal long axis on Day 24 showing diffuse banding late gadolinium enhancement in the basal-mid segments (A, B: arrows).

Discussion

Active cortisol is transformed to inactive cortisone in the kidney by 11βHDS2, and glycyrrhetinic acid, which is a component of liquorice, inhibits its enzymatic activity.² Liquorice overconsumption leads to the over-activation of mineralocorticoid receptors by cortisol in the kidney and subsequently causes hypokalaemia and hypertension, known as pseudoaldosteronism, based on these biochemical mechanisms.⁴ Herbal medicine is more frequently used in daily clinical practice in Japan than in Western countries.⁵ Shakuyakukanzoto, which contains liquorice, is often prescribed for muscle pain for older people in orthopaedics clinics, leading to frequent pseudoaldosteronism caused by its excessive intake.⁶ Yokukansan, which also contains liquorice, is often prescribed for irritability and insomnia and can cause pseudoaldosteronism.⁷ The present case was separately prescribed shakuyakukanzoto and yokukansan by two different clinics, which led to an unexpected excessive intake of liquorice. However, hypokalaemia and renin suppression are reported to occur in pseudoaldosteronism based on an individual’s sensitivity to glycyrrhizin, rather than being dose-dependent.⁸ A previous study has demonstrated low body weight as a predisposing factor for liquorice-induced pseudoaldosteronism.⁸ Hence, low body weight likely predisposes the current case to develop pseudoaldosteronism. Administration of herbal medicine containing liquorice to elderly patients with low body weight should be more careful.

Acute heart failure caused by excessive liquorice ingestion has been rarely described. Massive fluid infusion for acute renal injury caused by rhabdomyolysis could have triggered congestive heart failure and pulmonary oedema in the current case.⁹ Rhabdomyolysis might have induced massive catecholamine release leading to LV dysfunction, also known as takotsubo cardiomyopathy.¹⁰ However, the cardiac MRI findings and TTE findings of diffuse LV dysfunction without focal motion abnormality in the present case were inconsistent with takotsubo cardiomyopathy. Moreover, considering no elevation of troponin I and CK-MB, we have excluded acute myocardial infarction. To our knowledge, this is the first report to describe cardiac MRI findings in liquorice-induced pseudoaldosteronism accompanied by acute heart failure.

To obtain early recognition of acute heart failure development, serial evaluation of BNP level and LV function on TTE could be critical. Despite diffuse myocardial fibrosis indicated by LGE on the MRI findings,¹¹ the short-time recovery of LV function could be possible in a patient with pseudoaldosteronism and LV dysfunction. Multidisciplinary approach, including cardiologist and endocrinologist, is essential for the better management of this complex disease.

Conclusion

In conclusion, LV dysfunction in acute heart failure caused by liquorice-induced pseudoaldosteronism could be dramatically reversible for a short time despite myocardial fibrosis in the cardiac MRI.

Lead author biography

Dr Shinya Ito graduated from Shiga University of Medical Science and started his career in Kobe City Medical Center General Hospital, Kobe, Japan. After training in the Department of Cardiovascular Medicine, Kokura Memorial Hospital for four years, he is a general cardiology physician in Cardiovascular Centre, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan since 2020.

Supplementary material

Supplementary material is available at European Heart Journal – Case Reports

Consent: Written informed consent was obtained from the patient in line with the COPE guidelines for the submission and publication of this report, including images and associated text.

Funding: None.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.