Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia

Introduction

Liquorice intoxication is a well-known exogenous cause of hypokalaemia [1]. The active components of liquorice, glycyrrhizic acid and glycyrrhetinic acid, can cause an apparent mineralocorticoid excess syndrome due to the inhibition of the cortisol-converting enzyme 11-β-dehydrogenase [1, 2]. In previous reports on cases with pronounced abuse of liquorice candy, the resulting hypokalaemia produced myopathy and cardiac dysrhythmias, but to our knowledge, life-threatening ventricular tachycardia of torsades de pointes type was not previously found [3, 4].

Case report

The patient was a woman born in 1953 who had chronic pain of the back, neck and shoulders. She had otherwise been in good health and she took no regular medication. During the last month before admission to hospital the patient had occasionally experienced palpitations. Moreover, anaemia due to iron deficiency had recently been diagnosed and iron supplementation was started. On 29 March 1997 she attended the emergency unit at our university hospital due to irregular cardiac rhythm and a feeling of faintness for 4 days. On physical examination she appeared to be in good general condition. The blood pressure was 150/70. Heart auscultation disclosed an irregular rhythm with modest tachycardia. ECG showed sinus rhythm with frequent ventricular extrasystoles originating from several foci and sometimes clustered into short periods of ventricular tachycardia. The ventricular rate was ≈ 120–130 min^–1. The QT interval was prolonged, and the QT_c (corrected for the R–R interval) was 0.45–0.48 s in different recordings (normal ≤ 0.43 s) as shown in Fig. 1(a). The patient was transferred to the cardiac intensive care unit. Cardiac enzymes, i.e. lactate dehydrogenase and creatine phosphokinase, including their myocardial isoforms, were normal. Haemoglobin was 82 (normal range 119–153) g L^–1 and erythrocyte MCV was low. Analysis of serum electrolytes displayed low potassium, 2.3 (3.4–5.0) mmol L^–1, and a slightly reduced chloride, 97 (100–110) mmol L^–1. Serum phosphate was also slightly low at 0.77 (0.86–1.54) mmol L^–1. Total serum carbonate was in the upper normal range, 31 (23–32) mmol L^–1, whereas sodium, calcium and creatinine were all normal. Cardiac ultrasonography showed a normal myocardial function. Infusion with 40 mmol potassium and 5 mmol magnesium was administered during 2 hours. Despite this, the ventricular extrasystoles persisted and, moreover, the patient had at least five episodes with ventricular tachycardia of torsades de pointes type lasting up to 10 s ( Fig. 1b). The heart rate was then 250–300 min^–1 and some of these episodes were accompanied by unconsciousness and marked hypotension. Intravenous lidocain was given and the potassium/magnesium infusion was repeated. She also received a blood transfusion. The arrythmias eventually ceased after a few hours. A potassium infusion was then continued during the next 3 days and serum potassium gradually increased to 3.7 mmol L^–1. The QT_c, however, remained prolonged, and on 31 March it was 0.51 s. The patient had borderline hypertension with systolic and diastolic pressures of 150–160 and 90–100 mmHg, respectively. During the following days the patient was treated with metoprolol (Seloken Zoc^®) 100 mg daily and also with amiloride (Midamor^®) 15 mg daily as a potassium-sparing agent.

We wished to examine whether any endocrine disorder causing hypokalaemia was present. Twenty-four hour urine cortisol excretion was normal, 335 and 196 nmol per 24 h, respectively on two separate days (normal range 37–341). Urine aldosterone was low at < 4.2 nmol L^–1. Plasma renin was low, 0.03 (0.04–0.60) pkat L^–1, and so was plasma aldosterone, 122 (140–540) pmol L^–1, whereas the aldosteron/renin ratio was normal, at 4066 (< 5000). Thus, there was no indication of Cushing’s syndrome or of primary or secondary hyperaldosteronism. The patient denied any use of diuretics or laxatives which could be possible exogenous causes of hypokalaemia. She had no history of anorexia or vomiting and her body weight was normal at 62 kg. The patient had noted somewhat looser stools than previously. To examine whether a villous adenoma could be the cause of the hypokalaemia and anaemia, a colon endoscopy was performed. Three small hyperplastic polyps were identified and removed but no other abnormalities were found. Endoscopies of the oesophagus, ventricle and duodenum were normal. Faeces haemoglobin was negative. After 1 week in hospital the serum potassium had gradually increased to 5.9 mmol L^–1 and blood pressure decreased to normal levels. Amiloride and metoprolol treatment was stopped. A 24 h HOLTER ECG was performed on 8 April and, except for a short supraventricular tachycardia, the patient had a normal sinus rhythm. However, the QT_c was still modestly prolonged at 0.46 s. The patient was discharged from hospital the same day as she did not want to stay any longer. After another week, serum potassium was 4.1 mmol L^–1 without any treatment.

An ECG on 18 April showed regular sinus rhythm but the QT_c time had decreased to 0.44 s, i.e. just above the normal limit. On clinical follow-up at the end of May, the patient reported no cardiac symptoms. Blood pressure was normal (140/80) without any antihypertensive medication. Serum potassium was normal at 4.8 mmol L^–1. Blood haemoglobin was also normal (129 g L^–1), and after a gynaecological consultation the previous sideropenic anaemia was considered to be caused by large menstruations. On repeated questioning concerning exogenous causes of hypokalaemia it became clear that the patient had ingested ≈ 40–70 g of liquorice candy every day for approximately 4 months prior to hospitalization. She had quit this habit during the hospitalization period. We were not able to identify any other cause of the patient’s hypokalaemia and dysrhythmia.

An ECG examination in November 1997 displayed regular sinus rhythm, normal QRS complexes and also a normal QT time (QT_c = 0.42 s). At present, more than 1 year after hospitalization, the patient has not experienced any further significant cardiac symptoms and there are no signs of heart disease.

Discussion

This patient experienced a life-threatening ventricular tachycardia due to hypokalaemia, which was apparently caused by ingestion of relatively large amounts of liquorice. The active components of liquorice, glycyrrhizic acid and glycyrrhetinic acid, can cause an apparent mineralocorticoid excess syndrome due to the inhibition of the cortisol-converting enzyme 11-β-dehydrogenase [1, 2]. This enzyme can normally also prevent cortisol from interacting with the mineralocorticoid receptor. Liquorice abuse can thus lead to enhanced cortisol action on the mineralocorticoid receptor in the distal tubuli of the kidneys. This will promote potassium excretion and sodium and water retention, leading to hypokalaemia and hypertension, respectively [1, 2], and this was also seen in our patient. Peripheral oedema may occur and the hypokalaemia may lead to muscle pain and weakness, tetany, paraesthesiae, headaches and cardiac dysrhythmias. A compensatory suppression of plasma renin and aldosterone is common, as was found in the present case.

Torsades de pointes tachycardia is often associated with hypokalaemia and possibly concomitant hypomagnesaemia [5, 6]. We found no indication of other underlying perturbations in our patient, e.g. hereditary long QT interval syndrome, other cardiac disorders or use of proarrhythmic drugs apart from liquorice. However, the patient’s anaemia may possibly have been a contributing factor for the dysrhythmia. There may possibly be other unknown factors making this particular patient vulnerable to liquorice toxicity. For example, mutations in the 11-β-dehydrogenase type II enzyme may compromise its protective action on cortisol access to the mineralocorticoid receptor [7], and this might possibly lead to a greater sensitivity to liquorice action. Previous reports on intoxication with liquorice candy have documented severe hypokalaemia-associated myopathy and some instances of cardiac dysrhythmia [3, 4], but to our knowledge life-threatening ventricular tachycardia of torsades de pointes type has not previously been reported. However, in one earlier case [8], torsades de pointes was precipitated by ingestion of a Chinese herbal remedy containing an extract of the plant Glycyrrhiza glabra, the root of which is also used in the manufacture of liquorice. This supports the conclusion that liquorice was the cause of the dysrhythmia in our case. The fact that the perturbations in our patient, i.e. hypokalaemia, dysrhythmia and high blood pressure, were all normalized upon liquorice cessation also strongly suggests that liquorice was the major culprit.

In summary, this case report illustrates that it is important to keep liquorice in mind in cases with dysrhythmia and hypokalaemia of unknown cause. In our opinion, people should be advised not to repeatedly consume liquorice over a prolonged period of time, even at moderate levels .